1.1 ARY-CH-C(ALH)-NO2 to ARY-CH2-CH(ALH)-NO2 [Reaxys, All Reactions (375), Sort by MW of pro by Asch

Query Query 1. Query

NO 2 ARY

NO 2

ARY ALH

ALH

Results

Date

375 reactions in Reaxys

2017-08-15 22h:07m:23s (EST)

Search as: As drawn, No salts, No mixtures

1/143

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O N

N O

Rx-ID: 305120 View in Reaxys 1/375 Yield 100 %

Conditions & References With polymer-bound NADH (2a) Dupas, G.; Bourguignon, J.; Ruffin, C.; Queguiner, G.; Tetrahedron Letters; vol. 23; nb. 49; (1982); p. 5141 5144 View in Reaxys

100 %

With tri(1-naphthyl)phosphonium tris(pentafluorophenyl)borohydride in dichloromethane-d2, Time= 12h, Glovebox, Sealed tube, Reagent/catalyst Dupré, Jonathan; Gaumont, Annie-Claude; Lakhdar, Sami; Organic Letters; vol. 19; nb. 3; (2017); p. 694 - 697 View in Reaxys

> 99 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 0.166667h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

95 %

With poly(p-aminostyrene)-palladium(II), hydrogen in N,N-dimethyl-formamide, T= 25 °C , p= 760Torr Mukherjee, Debkumar; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 42; nb. 2; (2003); p. 346 - 352 View in Reaxys

95 %

With 1,4-diaza-bicyclo[2.2.2]octane, tris(2,4,6-trifluorophenyl)borane triethylphosphine oxide, Time= 24h, T= 50 °C , p= 3750.38Torr , Inert atmosphere Nicasio, Juan A.; Steinberg, Sebastian; Ines, Blanca; Alcarazo, Manuel; Chemistry - A European Journal; vol. 19; nb. 33; (2013); p. 11016 - 11020 View in Reaxys

93 %

With 2,6-dimethylpyridine, C18H9BF6*C4H8O, hydrogen in dichloromethane-d2, Time= 36h, T= -196.16 - 40 °C , p= 3000.3Torr , Inert atmosphere, Schlenk technique, Glovebox, Concentration, Time Greb, Lutz; Daniliuc, Constantin-Gabriel; Bergander, Klaus; Paradies, Jan; Angewandte Chemie - International Edition; vol. 52; nb. 22; (2013); p. 5876 - 5879; Angew. Chem.; vol. 125; nb. 22; (2013); p. 5989 - 5992,4 View in Reaxys

91 %

With 2,6-dimethyl-3,5-diacetyl-1,4-dihydropyridine, silica gel in dichloromethane, microwave irradiation Torchy, Severine; Cordonnier, Guy; Barbry, Didier; Vanden Eynde, Jean Jacques; Molecules; vol. 7; nb. 7; (2002); p. 528 - 533 View in Reaxys

2/143

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91 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 1h, T= 20 °C Astolfi, Paola; Charles, Laurence; Gigmes, Didier; Greci, Lucedio; Rizzoli, Corrado; Sorana, Federico; Stipa, Pierluigi; Organic and Biomolecular Chemistry; vol. 11; nb. 8; (2013); p. 1399 - 1406 View in Reaxys

90 %

88 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 - 5 °C , other non-α-substituted nitroalkenes Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

88 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 °C , other monosubstituted nitroalkenes, Mechanism Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys

88 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 - 5 °C Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

88 %

With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, Time= 1h, Heating Chikashita, Hidenori; Morita, Yasuhiro; Itoh, Kazuyoshi; Synthetic Communications; vol. 15; nb. 6; (1985); p. 527 - 534 View in Reaxys

88 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 °C Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys

88 %

With sodium tetrahydroborate in tetrahydrofuran, methanol Vo, Quan V.; Trenerry, Craige; Rochfort, Simone; Wadeson, Jenny; Leyton, Carolina; Hughes, Andrew B.; Bioorganic and Medicinal Chemistry; vol. 21; nb. 19; (2013); p. 5945 - 5954 View in Reaxys

85 %

With nickel(II) ferrite, isopropyl alcohol, Time= 3h, T= 80 °C , Green chemistry, Reagent/catalyst, Temperature Payra, Soumen; Saha, Arijit; Banerjee, Subhash; RSC Advances; vol. 6; nb. 57; (2016); p. 52495 - 52499 View in Reaxys

84 %

With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h Cherest, M.; Lusinchi, X; Tetrahedron; vol. 42; nb. 14; (1986); p. 3825 - 3840 View in Reaxys

82 %

With hydrogen in ethanol, Time= 24h, T= 20 °C , p= 760.051Torr , chemoselective reaction

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Hagiwara, Hisahiro; Nakamura, Tomomi; Hoshi, Takashi; Suzuki, Toshio; Green Chemistry; vol. 13; nb. 5; (2011); p. 1133 - 1137 View in Reaxys 81 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Tarnus, Celine; Remy, Jean-Marc; D'Orchymont, Hugues; Bioorganic and Medicinal Chemistry; vol. 4; nb. 8; (1996); p. 1287 - 1297 View in Reaxys

80 %

With tert-butyl 2-(2-(phenylcarbamothioyl)hydrazinecarbonyl)pyrrolidine-1-carboxylate, diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate in dichloromethane Liu, Wen-Xia; Yang, Rui; Li, Ai-Fang; Li, Zhao; Gao, Yu-Feng; Luo, Xing-Xing; Ruan, Yi-Bin; Jiang, Yun-Bao; Organic and Biomolecular Chemistry; vol. 7; nb. 19; (2009); p. 4021 - 4028 View in Reaxys

80 %

2 : Reduction of nitro compound by resin-AuNPs General procedure: In a typical reduction protocol, 100 mg of catalyst was added to 20 mL of methanol/water (1:1) solution containing 0.5 mmol of nitro compound and 5 mmol of NaBH4. The mixture was vigorously stirred at 40°C. The reaction was monitored by Thin Layer Chromatography (TLC) and reaction mixture was quenched by extracting the organic derivatives with ethyl acetate. The solvent was evaporated under vacuum to give crude product of corresponding amine compound. Further purification was done through column chromatography. The products were confirmed by their melting points and 1H NMR spectroscopy. With sodium tetrahydroborate in methanol, water, Time= 0.5h, T= 40 °C Shah, Dipen; Kaur, Harjinder; Journal of Molecular Catalysis A: Chemical; vol. 381; (2014); p. 70 - 76 View in Reaxys

78 %

With L-Selectridereg; in tetrahydrofuran, Ambient temperature Kabalka, George W.; Laila Guindi; Varma, Rajender S.; Tetrahedron; vol. 46; nb. 21; (1990); p. 7443 - 7457 View in Reaxys

77 %

With magnesium(II) perchlorate in acetonitrile, Time= 96h Cazin, J.; Trefouel, T.; Dupas, G.; Bouguignon, J.; Queguiner, G.; Tetrahedron; vol. 44; nb. 4; (1988); p. 1079 1090 View in Reaxys

70 %

With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h, T= 25 °C Battersby, Alan R.; Baker, Mark G.; Broadbent, Hugo A.; Fookes, Christopher J. R.; Leeper, Finian J.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1987); p. 2027 2048 View in Reaxys

69 %

With sodium tetrahydroborate, silica gel in i-Amyl alcohol, chloroform, Time= 2h, T= 20 °C , Inert atmosphere Manna, Madhu Sudan; Mukherjee, Santanu; Journal of the American Chemical Society; vol. 137; nb. 1; (2015); p. 130 - 133 View in Reaxys

64 %

With sodium tetrahydroborate in chloroform, isopropyl alcohol, T= 0 - 20 °C Han, Xiaoyu; Dong, Li; Geng, Caiwei; Jiao, Peng; Organic Letters; vol. 17; nb. 13; (2015); p. 3194 - 3197 View in Reaxys

17 %

With hydrogen, rhodium(III) chloride, RhCl3-Aliquat 336 in 1,2-dichloro-ethane, Time= 22h

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Amer, Ibrahim; Bravdo, Tamar; Blum, Jochanan; Vollhardt, K. Peter C.; Tetrahedron Letters; vol. 28; nb. 12; (1987); p. 1321 - 1322 View in Reaxys 100 % Chromat.

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, acetic acid in benzene, Time= 15h, T= 80 °C , different acetic acid amount; competitive reaction with cinnamaldehyde, Product distribution Inoue, Yoshio; Imaizumi, Shin; Itoh, Hiromitsu; Shinya, Takao; Hashimoto, Harukichi; Miyano, Sotaro; Bulletin of the Chemical Society of Japan; vol. 61; (1988); p. 3020 - 3022 View in Reaxys With tetrahydrofuran, lithium borate, diethyl ether Shechter et al.; Journal of the American Chemical Society; vol. 78; (1956); p. 4984,4985 View in Reaxys With hydrogenchloride, tin(ll) chloride in methanol, T= -15 - -10 °C Dornow,A.; Mueller,A.; Chemische Berichte; vol. 93; (1960); p. 32 - 40 View in Reaxys With Wilkinson's catalyst, hydrogen Birch,A.J.; Walker,K.A.M.; Journal of the Chemical Society [Section] C: Organic; (1966); p. 1894 - 1896 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1) methylene chloride, room temp., 20h, 2) methanol, -15 deg C, Yield given. Multistep reaction Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1.) methylene chloride, 20-24h, room temperature; 2.) MeOH, methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys With magnesium(II) perchlorate, 1-Benzyl-1,4-dihydronicotinamide in acetonitrile, T= 80 °C , Yield given Tintillier, P.; Dupas, G.; Bourguignon, J.; Queguiner, G.; Tetrahedron Letters; vol. 27; nb. 21; (1986); p. 2357 2360 View in Reaxys With silica gel, L-Selectridereg;, 1.) THF, RT, 30 min, Yield given. Multistep reaction Varma, Rajender S.; Kabalka, George W.; Synthetic Communications; vol. 14; nb. 12; (1984); p. 1093 - 1098 View in Reaxys

100 % Chromat.

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, acetic acid in benzene, Time= 15h, T= 80 °C Inoue, Yoshio; Imaizumi, Shin; Itoh, Hiromitsu; Shinya, Takao; Hashimoto, Harukichi; Miyano, Sotaro; Bulletin of the Chemical Society of Japan; vol. 61; (1988); p. 3020 - 3022 View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, T= 20 °C Vaidya, Vipraja V.; Wankhede, Karuna S.; Nara, Susheel J.; Salunkhe, Manikrao M.; Trivedi, Girish K.; Synthetic Communications; vol. 39; nb. 21; (2009); p. 3856 - 3866 View in Reaxys With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, T= 20 °C , Inert atmosphere, Reflux Zhang, Fanglin; Wei, Mohui; Dong, Junfang; Zhou, Yirong; Lu, Dengfu; Gong, Yuefa; Yang, Xiangliang; Advanced Synthesis and Catalysis; vol. 352; nb. 17; (2010); p. 2875 - 2880 View in Reaxys

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With C14H9N2O2Rh, hydrogen in N,N-dimethyl-formamide Sagar, Priyanka; Rani, Varsha; Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry; vol. 40; nb. 10; (2010); p. 754 - 761 View in Reaxys 2.3. Catalytic, recycling and kinetic experiments Unless specified otherwise, all hydrogenation reactions were carried out at 353 K in small glass vials placed inside a 200-mL autoclave with vigorous magnetic stirring (P900 RPM). Conversions and selectivities were measured by 1H NMR and gas chromatographic techniques. All hydrogenated products were initially identified by using authentic commercial samples of the expected products. The recycling experiments with 1 and 2 were carried out at 353 K under 50 and 40 bar H2 pressure, respectively, with a substrate-to-Ru molar ratio of 283 and 625 in 5 mL of methanol and water, respectively. Recycling experiments with 2 covering five successive batches were also carried out with styrene as the substrate, with a styrene-to-Ru molar ratio of 625 in 5 mL of methanol. Catalyst 1 was filtered off, washed several times with methanol, and used for the second batch. For the reaction with 2, the product was separated from the aqueous solution by ethyl acetate extraction(2 x 10 mL). The aqueous solution of 2 was then reused. A few recycling experiments were also carried out, where 2 was precipitated from the water solution by the addition of acetone and reused. The results obtained by both these methods of catalyst recovery were comparable. With hydrogen in methanol, water, Time= 12h, T= 79.84 °C , p= 37503.8Torr , chemoselective reaction Indra, Arindam; Maity, Niladri; Maity, Prasenjit; Bhaduri, Sumit; Lahiri, Goutam Kumar; Journal of Catalysis; vol. 284; nb. 2; (2011); p. 176 - 183 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhao, Xinyang; Wang, Xinbo; Liu, Qisong; Li, Zigang; Wang, David Zhigang; Angewandte Chemie - International Edition; vol. 51; nb. 32; (2012); p. 8050 - 8053 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys 100 With hydrogen in n-heptane, Time= 2h, T= 20 °C , p= 2068.65Torr , Autoclave, chemoselective reaction %Chromat. Natour, Suzana; Abu-Reziq, Raed; RSC Advances; vol. 4; nb. 89; (2014); p. 48299 - 48309 View in Reaxys

O N

O N O

Rx-ID: 940329 View in Reaxys 2/375 Yield 100 %

Conditions & References With magnesium(II) perchlorate, model of NADH grafted on silica matrix in acetonitrile, Time= 120h, T= 65 °C Bourguignon, Jean; Tintillier, Patrick; Trefouel, Thierry; Losset, Denis; Dupas, Georges; Queguiner, Guy; Bulletin de la Societe Chimique de France; nb. 2; (1989); p. 264 - 266 View in Reaxys

98 %

With hydrogen, tris(triphenylphosphine)rhodium(l) chloride in benzene, Time= 14h, T= 50 °C , p= 2585.81Torr Patent; WARNER-LAMBERT COMPANY; EP1203767; (2002); (A1) English View in Reaxys

96 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, silica gel in benzene, Time= 20h, T= 60 °C Nakamura, Kaoru; Fujii, Masayuki; Oka, Shinzaburo; Ohno, Atsuyoshi; Chemistry Letters; (1985); p. 523 - 526 View in Reaxys

96 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 2h, T= 100 °C , neat (no solvent)

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Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys 96 %

95 %

With [(COD)Ir(dimethylphenylphosphine)(1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene)](tetrakis(3,5-bis(trifluoromethyl)phenyl)borate), hydrogen in dichloromethane, Time= 16h, T= -78 - 25 °C , p= 760.051Torr , chemoselective reaction Kerr, William J.; Mudd, Richard J.; Brown, Jack A.; Chemistry - A European Journal; vol. 22; nb. 14; (2016); p. 4738 - 4742 View in Reaxys

93 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.416667h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

89 %

With formic acid, triethylamine, N-tosylethylenediamine, [(η6-p-MeC6H4Pri)2Ru2Cl2(μ-Cl)2] in dichloromethane, Time= 4h, T= 30 °C Xue, Dong; Chen, Ying-Chun; Cui, Xin; Wang, Qi-Wei; Zhu, Jin; Deng, Jin-Gen; Journal of Organic Chemistry; vol. 70; nb. 9; (2005); p. 3584 - 3591 View in Reaxys

88 %

With (3,5-(CF3)2C6H3NH)2C=S, 2,6-di(Me)-1,4-dihydropyridine-3,5-di(COOEt) in dichloromethane, Time= 24h, T= 50 °C Zhang, Zhiguo; Schreiner, Peter R.; Synthesis; nb. 16; (2007); p. 2559 - 2564 View in Reaxys

84 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, silica gel in benzene, Time= 17h, T= 80 °C Nakamura, Kaoru; Fujii, Masayuki; Ohno, Atsuyoshi; Oka, Shinzaburo; Tetrahedron Letters; vol. 25; nb. 36; (1984); p. 3983 - 3986 View in Reaxys

84 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys

84 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, silica gel in benzene, Time= 0.5h, Heating FUJI, Masayuki; Bulletin of the Chemical Society of Japan; vol. 61; nb. 11; (1988); p. 4029 - 4036 View in Reaxys

84 %

With silica gel in benzene, Time= 5h, Heating, dark Fujii; Nakamura; Yasui; et al.; Bulletin of the Chemical Society of Japan; vol. 60; nb. 7; (1987); p. 2423 - 2427 View in Reaxys

81 %

With hydrogen, nitrobenzene in 1,4-dioxane, Time= 24h, T= 20 °C Huang, Lei; Luo, Pingfei; Pei, Weige; Liu, Xiaoyun; Wang, Yong; Wang, Jun; Xing, Weihong; Huang, Jun; Advanced Synthesis and Catalysis; vol. 354; nb. 14-15; (2012); p. 2689 - 2694 View in Reaxys

80 %

With 2-phenylthiazoline, iron(III) chloride, aluminium trichloride, Heating, 1.) BuOH, 24 h, reflux, 2.) MeOH, 40 deg C, 4 h

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Chikashita, Hidenori; Miyazaki, Makoto; Itoh, Kazuyoshi; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1987); p. 699 - 706 View in Reaxys 80 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, C44H54N10O8S in chloroform-d1, T= 35 °C , Michael addition Ajami, Dariush; Kamioka, Seiji; Sather, Aaron C.; Hooley, Richard J.; Rebek Jr., Julius; Heterocycles; vol. 82; nb. 2; (2011); p. 1203 - 1215 View in Reaxys

75 %

With sodium cyanoborohydride, zeolite H-ZSM5 in methanol, Time= 1h, pH 6.5 Gupta, Anuradha; Haque, Azizul; Vankar, Yashwant D.; Chemical Communications; nb. 14; (1996); p. 1653 1654 View in Reaxys

74 %

72 %

With Mauripan Instant Dry Yeast, water in Petroleum ether, Time= 24h, Ambient temperature McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys

48 %

With sodium tetrahydroborate in tetrahydrofuran, ethanol, Time= 12.33h, T= 0 °C Sakai, Norio; Sasaki, Minoru; Ogiwara, Yohei; Chemical Communications; vol. 51; nb. 58; (2015); p. 11638 11641 View in Reaxys

43 %

in water, Time= 72h, T= 31 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

26 %

With D-glucose, bakers' yeast in ethanol, water, Time= 48h, Ambient temperature, pH 8 Ohta, Hiromichi; Kobayashi, Naoki; Ozaki, Kazuhiko; Journal of Organic Chemistry; vol. 54; nb. 8; (1989); p. 1802 - 1804 View in Reaxys

20 %

With phenylsilane, oxygen, Mn(dpm)3 in isopropyl alcohol, Time= 4h, T= 0 - 20 °C Magnus, Philip; Scott, David A.; Fielding, Mark R.; Tetrahedron Letters; vol. 42; nb. 25; (2001); p. 4127 - 4129 View in Reaxys With lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether, T= -45 - -40 °C Dore; Viel; Farmaco, Edizione Scientifica; vol. 30; nb. 2; (1975); p. 81 - 109 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol Burkhart, Joseph P.; Peet, Norton P.; Bey, Philippe; Tetrahedron Letters; vol. 29; nb. 28; (1988); p. 3433 - 3436 View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.25h, T= 25 °C Kodukulla; Trivedi; Vora; Mathur; Synthetic Communications; vol. 24; nb. 6; (1994); p. 819 - 832 View in Reaxys

2.86 g

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.25h

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Chatterjee, Sankar; Ator, Mark A.; Bozyczko-Coyne, Donna; Josef, Kurt; Wells, Gregory; Tripathy, Rabindranath; Iqbal, Mohamed; Bihovsky, Ron; Senadhi, Shobha E.; Mallya, Satish; O'Kane, Teresa M.; McKenna, Beth Ann; Siman, Robert; Mallamo, John P.; Journal of Medicinal Chemistry; vol. 40; nb. 23; (1997); p. 3820 3828 View in Reaxys With 1,3-bis-(diphenylphosphino)propane, caesium carbonate, benzyl alcohol, bis(1,5-cyclooctadiene)diiridium(I) dichloride in toluene, Time= 24h, T= 150 °C Black, Phillip. J.; Cami-Kobeci, Gerta; Edwards, Michael G.; Slatford, Paul A.; Whittlesey, Michael K.; Williams, Jonathan M. J.; Organic and Biomolecular Chemistry; vol. 4; nb. 1; (2006); p. 116 - 125 View in Reaxys 129.a : (a) (a) 2-Phenylnitroethane A mixture of (trans)-β-Nitrostyrene (50.0 g, 0.335 mol), tris(triphenylphosphine)rhodium(I) chloride (10.7 g) and benzene (500 mL) at 50° C. was shaken under hydrogen at 50 psi for 14 hours and allowed to cool. The solution was rotoevaporated, suspended in petroleum ether-ether (9:1), and gravity filtered through a plug of fluorisil (80 g)/silica gel (300 g). The filtrate was rotoevaporated to a pale yellow oil; yield (49.5 g, 98percent). 1 H NMR (CDCl ): δ7.2-7.4 (m, 5H), 4.6 (t, 2H), 3.3 (t, 2H) ppm. 3 With RhCl(PPh3)3 in petroleum ether-ether, benzene Patent; Warner-Lambert Company; US5366987; (1994); (A1) English View in Reaxys With glucose-6-phosphate, pentaerythritol tetranitrate reductase, NADP+, glucose 6-phosphate dehydrogenase, T= 25 °C , pH= 7, aq. phosphate buffer, Inert atmosphere, Enzymatic reaction, Kinetics Toogood, Helen S.; Fryszkowska, Anna; Hare, Victoria; Fisher, Karl; Roujeinikova, Anna; Leys, David; Gardiner, John M.; Stephens, Gill M.; Scrutton, Nigel S.; Advanced Synthesis and Catalysis; vol. 350; nb. 17; (2008); p. 2789 - 2803 View in Reaxys With C49H64N10O3S, diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate in chloroform-d1, Time= 144h, T= 0 20 °C Kamioka, Seiji; Ajami, Dariush; Rebek Jr., Julius; Chemical Communications; nb. 47; (2009); p. 7324 - 7326 View in Reaxys With wild type Salmonella typhimurium nitroreductase, Enzymatic reaction Yanto, Yanto; Hall, Melanie; Bommarius, Andreas S.; Organic and Biomolecular Chemistry; vol. 8; nb. 8; (2010); p. 1826 - 1832 View in Reaxys With glucose dehydrogenase, D-glucose, xenobiotic reductase A C25G mutant, NADPH, pH= 7.5, aq. phosphate buffer Yanto, Yanto; Yu, Hua-Hsiang; Hall, Melanie; Bommarius, Andreas S.; Chemical Communications; vol. 46; nb. 46; (2010); p. 8809 - 8811 View in Reaxys With Fe(acac)3, 1,1,3,3-Tetramethyldisiloxane in tetrahydrofuran, Time= 24h, T= 60 °C , Inert atmosphere, Sealed tube Pehlivan, Leyla; Metay, Estelle; Laval, Stephane; Dayoub, Wissam; Demonchaux, Patrice; Mignani, Gerard; Lemaire, Marc; Tetrahedron; vol. 67; nb. 10; (2011); p. 1971 - 1976 View in Reaxys With xenobiotic reductase B from Pseudomonas putida JLR11, NADH in tert-butyl methyl ether, Time= 24h, T= 30 °C , pH= 7.5, aq. buffer, Enzymatic reaction

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Durchschein, Katharina; Fabian, Walter M. F.; MacHeroux, Peter; Zangger, Klaus; Trimmel, Gregor; Faber, Kurt; Organic and Biomolecular Chemistry; vol. 9; nb. 9; (2011); p. 3364 - 3369 View in Reaxys With D-glucose, ene-reductase KYE1 from genomic DNA of Kluyveromyces lactis ATCC 8585, nicotinamide adenine dinucleotide phosphate, Time= 12h, T= 20 °C , pH= 7.5, aq. phosphate buffer, Enzymatic reaction Yanto, Yanto; Winkler, Christoph K.; Lohr, Stephanie; Hall, Melanie; Faber, Kurt; Bommarius, Andreas S.; Organic Letters; vol. 13; nb. 10; (2011); p. 2540 - 2543 View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol Burkhard, Johannes A.; Tchitchanov, Boris H.; Carreira, Erick M.; Angewandte Chemie - International Edition; vol. 50; nb. 23; (2011); p. 5379 - 5382 View in Reaxys N O

Cl NH 2

O N O

Rx-ID: 1701052 View in Reaxys 3/375 Yield

Conditions & References

100 %

With anhydrous magnesium perchlorate, silice (Merck Kieselgel Art.:7734), multistep reaction; 1.) grafting on a silica matrix, reflux, in toluene, 12 h, 2.) reflux, toluene, 5 days. 3.) acetonitrile, 65 deg C, 5 days; reagent quqntity, reaction time varied, Product distribution Bourguignon, Jean; Tintillier, Patrick; Trefouel, Thierry; Losset, Denis; Dupas, Georges; Queguiner, Guy; Bulletin de la Societe Chimique de France; nb. 2; (1989); p. 264 - 266 View in Reaxys

O O

O N O

Rx-ID: 1986975 View in Reaxys 4/375 Yield

Conditions & References

10 %

With tri-n-butyl-tin hydride, 3-chloro-benzenecarboperoxoic acid, 1.) methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys

O N

Rx-ID: 2062731 View in Reaxys 5/375 Yield

Conditions & References

10 %

With tri-n-butyl-tin hydride, ozone, 1.) methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys

Z N O

N O

Rx-ID: 3962074 View in Reaxys 6/375 Yield 88 %

Conditions & References With 2-phenyl dihydrobenzimidazole in butan-1-ol, Time= 1h, Heating, different solvents, other temperature and other p-substituted benzaldehydes, Product distribution

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Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys 88 %

With PBI in butan-1-ol, Time= 1h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

H 2N

O N

H 2N

Rx-ID: 24275141 View in Reaxys 7/375 Yield

Conditions & References

95%

219 : Isomer A: (+-)(cis) 4-methyl-5-(phenylmethyl)pyrrolidin-2-imine, monohydrochloride EXAMPLE 219 AND EXAMPLE 64 Isomer A: (+-)(cis) 4-methyl-5-(phenylmethyl)pyrrolidin-2-imine, monohydrochloride Isomer B: (+-) (trans) 4-methyl-5-(phenylmethyl)pyrrolidin-2-imine, monohydrochloride STR224 219 A) trans-b-Nitrostyrene (63.0 g, 0.42 mole) was reacted with benzaldehyde (53.4 g, 0.5 mole) and 1,2-diaminobenzene (54.4 g, 0.5 mole) according to the procedure of Chikashita et. al. (Synth. Commun. 1985, 15 (6), 527) to yield (2-nitroethyl)benzene (60.0 g, 95percent) as a yellow oil. With benzaldehyde Patent; G. D. Searle and Co.; US5883251; (1999); (A1) English View in Reaxys

95%

219 : Isomer B: (+-) (trans) 4-methyl-5-(phenylmethyl)pyrrolidin-2-amine, monohydrochloride STR224 Isomer B: (+-) (trans) 4-methyl-5-(phenylmethyl)pyrrolidin-2-amine, monohydrochloride STR224 Example 219 A) trans-b-Nitrostyrene (63.0 g, 0.42 mole) was reacted with benzaldehyde (53.4 g, 0.5 mole) and 1,2diaminobenzene (54.4 g, 0.5 mole) according to the procedure of Chikashita et. al. (Synth. Commun. 1985, 15 (6), 527) to yield (2-nitroethyl)benzene (60.0 g, 95percent) as a yellow oil. With benzaldehyde Patent; G.D. Searle and Co.; US6011028; (2000); (A1) English View in Reaxys

O N

Rx-ID: 24645158 View in Reaxys 8/375 Yield 75%

Conditions & References 15.b : 15b. 15b. 2-phenylnitroethane 2-Phenylnitroethene (5.12 g, 34.3 mmol, from step 15a) was dissolved in CHCl3 /i-PrOH (410:85 mL) and SiO2 (51.4 g) was added. NaBH4 (5.2 g, 137 mmol) was added in portions, and the mixture was stirred for 90 minutes at room temperature. HCl (0.5N, 100, mL) was added, and the mixture was stirred for 30 minutes. The layers were separated, and the aqueous phase was extracted with methylene chloride. The organic layers were combine, dried (MgSO4) and concentrated. The residue was chromatographed on silica gel (eluding with ether:hexanes 1:30) to give the title compound as an oil (3.89 g, 75percent). With hydrogenchloride, sodium tetrahydroborate, Nalco silica sol 1060 in chloroform Patent; Abbott Laboratories; US5733912; (1998); (A1) English View in Reaxys

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10-Cyano-2-cyclopentyl-decanoyl-Ng -nitro-L-arginyl-phenylalanine fluoromethylketone

N O

O N O

Rx-ID: 24648555 View in Reaxys 9/375 Yield

Conditions & References 42.A : A) A) Synthesis of 1-Nitro-2-phenylethane To a stirring mixture of trans-β-nitrostyrene (5.25 g, 0.035 mol) and silica gel (10 g, 230-400 mesh) in chloroform (400 mL) and isopropanol (75 mL) at room temperature, was slowly added sodium borohydride (5.50 g, 0.145 mol) over a period of 45 min. The reaction mixture was stirred for an additional 15 min and then carefully quenched with 10percent hydrochloric acid (20 mL). Separated solid was filtered and washed with chloroform (50 mL). Combined filtrate and washing was washed with water (1*20 mL), brine (1*20 mL) and dried over anhydrous sodium sulfate. Solvent evaporation at reduced pressure gave a crude material which was purified by flash chromatography (silica gel, 8percent ethyl acetate-hexane) to give 2.86 g of 1-nitro-2-phenylethane as a colorless oil (spicy odor); Rf (10percent ethyl acetate in hexane): 0.40; 1 H-NMR (300 MHz, CDCl3) 7.40-7.20 (m, 5H), 4.60 (t, 2H), 3.30 (t, 2H). With sodium borohydride in chloroform, isopropyl alcohol Patent; Cephalon, Inc.; US5614649; (1997); (A1) English View in Reaxys 2H

O N

Rx-ID: 39417920 View in Reaxys 10/375 Yield

Conditions & References With [Ir(1,5-cyclooctadiene)(IMes)(PPh3)][PF6], deuterium in dichloromethane, Time= 1h, T= -78 - 25 °C , p= 760.051Torr , Inert atmosphere, regioselective reaction Kerr, William J.; Mudd, Richard J.; Paterson, Laura C.; Brown, Jack A.; Chemistry - A European Journal; vol. 20; nb. 45; (2014); p. 14604 - 14607 View in Reaxys O

N 2H

Rx-ID: 1701111 View in Reaxys 11/375 Yield

Conditions & References

93 %

With silica gel, 4,4-dideuterio-2,6-dimethyl-3,5-dicarboethoxy-l,4-dihydropyridine in benzene, Time= 0.5h, Heating FUJI, Masayuki; Bulletin of the Chemical Society of Japan; vol. 61; nb. 11; (1988); p. 4029 - 4036 View in Reaxys O

Z N

O O

N 2H

Rx-ID: 3962075 View in Reaxys 12/375 Yield 83 %

Conditions & References With PBI-1,3-d2 in acetonitrile, Time= 24h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746

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View in Reaxys

N O

Rx-ID: 3962076 View in Reaxys 13/375 Yield

Conditions & References

91 %

With PBI-2-d in butan-1-ol, Time= 1h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys 2H

Rx-ID: 4816969 View in Reaxys 14/375 Yield

Conditions & References

73 %

O N

Rx-ID: 4829139 View in Reaxys 15/375 Yield

Conditions & References With Mauripan Instant Dry Yeast, water in Petroleum ether, Time= 24h, Ambient temperature, Yield given. Yields of byproduct given. Title compound not separated from byproducts McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys O

O O

O N

Rx-ID: 4836714 View in Reaxys 16/375 Yield

Conditions & References With Mauripan Instant Dry Yeast, water in Petroleum ether, Ambient temperature McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys

O O

E 2H

N 2H

Rx-ID: 4836715 View in Reaxys 17/375 Yield

Conditions & References With sodium tetrahydroborate

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McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys O O

EtCu(CN)ZnI

N 2

Rx-ID: 16989927 View in Reaxys 18/375 Yield

Conditions & References Reaction Steps: 2 1: Mauripan Instant Dry Yeast, D2O / light petroleum / Ambient temperature 2: NaBH4 With sodium tetrahydroborate, Mauripan Instant Dry Yeast, water-d2 in Petroleum ether McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys O

N O

O N

O 2H

N O

Rx-ID: 4816968 View in Reaxys 19/375 Yield

Conditions & References With Mauripan Instant Dry Yeast, water-d2 in Petroleum ether, Ambient temperature, Yield given McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys

O O

Rx-ID: 269581 View in Reaxys 20/375 Yield > 99 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 0.5h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

91 %

90 %

4.2. Typical procedure for the reduction of conjugated nitroalkenes

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General procedure: The mixture of nitroalkenes 1 (0.1 g, 0.67 mmol), Hantzsch ester (0.19 g, 0.74 mmol) and Sbenzyl isothiouronium chloride (14 mg, 0.067 mmol) in methanol (5 ml) was stirred at 60 °C for 5-12 h. After completion of the reaction, the crude product in methanol was concentrated and added into the excess cooled CH2Cl2. The S-benzyl isothiouronium chloride was readily precipitated out, and then filtered and washed many times with CH2Cl2 to be reused. The filtrate was evaporated and the residue was purified by flash column chromatography to give the required nitroalkanes products 2. All nitroalkanes except 2j and 2p were characterized with the reported spectroscopic data. [2] and [5] With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, S-benzyl isothiouronium chloride in methanol, T= 60 °C , Inert atmosphere Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron; vol. 68; nb. 32; (2012); p. 6513 6516 View in Reaxys 84 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 12h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

83 %

82 %

With sodium tetrahydroborate in tetrahydrofuran, methanol, Time= 0.666667h, Ambient temperature, other conjugated nitroalkenes, Product distribution Kabalka, George W.; Laila Guindi; Varma, Rajender S.; Tetrahedron; vol. 46; nb. 21; (1990); p. 7443 - 7457 View in Reaxys

82 %

With sodium tetrahydroborate in tetrahydrofuran, methanol, Time= 0.666667h, Ambient temperature Kabalka, George W.; Laila Guindi; Varma, Rajender S.; Tetrahedron; vol. 46; nb. 21; (1990); p. 7443 - 7457 View in Reaxys Varma, Rajender S.; Kabalka, George W.; Synthetic Communications; vol. 15; nb. 2; (1985); p. 151 - 156 View in Reaxys

81 %

With borohydride supported ion exchange resin in methanol, Time= 1h, Ambient temperature Goudgaon, Naganna M.; Wadgaonkar, Prakash P.; Kabalka, George W.; Synthetic Communications; vol. 19; nb. 5and6; (1989); p. 805 - 812 View in Reaxys

70 %

51 %

With sodium tetrahydroborate in tetrahydrofuran, methanol, Time= 0.666667h, T= 20 °C Merlino, Alicia; Boiani, Mariana; Cerecetto, Hugo; Gonzalez, Mercedes; Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy; vol. 67; nb. 2; (2007); p. 540 - 549 View in Reaxys With palladium on activated charcoal, water, T= 35 °C , p= 25742.8Torr , Hydrogenation Patent; Comm. Solv. Corp.; US2483201; (1945) View in Reaxys With tetrahydrofuran, diethyl ether Shechter et al.; Journal of the American Chemical Society; vol. 78; (1956); p. 4984,4985

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View in Reaxys With lithium aluminium tetrahydride, diethyl ether Gilsdorf; Nord; Journal of the American Chemical Society; vol. 74; (1952); p. 1837,1841 View in Reaxys With hydrogenchloride, tin(ll) chloride in methanol, T= -5 °C Dornow,A.; Mueller,A.; Chemische Berichte; vol. 93; (1960); p. 32 - 40 View in Reaxys With formic acid, triethylamine in N,N-dimethyl-formamide Nanjo,K.; Sekija,M.; Chemical and Pharmaceutical Bulletin; vol. 27; (1979); p. 198 - 203 View in Reaxys With sodium cyanoborohydride in ethanol Hutchins,R.O. et al.; Journal of Organic Chemistry; vol. 41; nb. 20; (1976); p. 3328 - 3329 View in Reaxys With tri-n-butyl-tin hydride, acetic acid, 1) methylene chloride, room temp., 24h, Yield given. Multistep reaction Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1.) methylene chloride, 20-24h, room temperature; 2.) MeOH, methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys With silica gel, L-Selectridereg;, 1.) THF, RT, 30 min, Yield given. Multistep reaction Varma, Rajender S.; Kabalka, George W.; Synthetic Communications; vol. 14; nb. 12; (1984); p. 1093 - 1098 View in Reaxys With wild type Salmonella typhimurium nitroreductase, Enzymatic reaction Yanto, Yanto; Hall, Melanie; Bommarius, Andreas S.; Organic and Biomolecular Chemistry; vol. 8; nb. 8; (2010); p. 1826 - 1832 View in Reaxys 94 %Spectr.

75 %Chromat.

With D-glucose, glucose dehydrogenase (GDH; 10U), holo-(flavin free double bond reductase from Nicotiana tabacum), nicotinamide adenine dinucleotide phosphate in aq. phosphate buffer, Time= 24h, T= 30 °C , pH= 6.4, Enzymatic reaction Mansell, David J.; Toogood, Helen S.; Waller, John; Hughes, John M.X.; Levy, Colin W.; Gardiner, John M.; Scrutton, Nigel S.; ACS Catalysis; vol. 3; nb. 3; (2013); p. 370 - 379 View in Reaxys Typical procedure for catalytic asymmetric hydrogenation General procedure: A 10mL tube equipped with a magnetic stirring bar, substrate (0.5mmol), catalyst (0.005mmol) and KOH (0.05mmol), was vacuum-pumped and flushed with argon three times. A degassed solvent (2mL) was then added and the tube was transferred to a stainless autoclave in a glove box. The autoclave was pressurized and evacuated with hydrogen three times, and finally charged with hydrogen at a pressure of 50atm. The reaction mixture was magnetically stirred at the given temperature for 24h. After cooling to room temperature, the pressure was released. The solvent was removed in vacuo and the crude product was examined by 1H NMR to determine the con-

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version. The pure product was obtained by flash column chromatography using ethyl acetate/petroleum ether as the eluant. With C17H33ClIrNP2, hydrogen, potassium hydoxide in methanol, Time= 24h, T= 25 °C , p= 38002.6Torr , Autoclave, Glovebox, enantioselective reaction Yang, Zehua; Wei, Xuan; Liu, Delong; Liu, Yangang; Sugiya, Masashi; Imamoto, Tsuneo; Zhang, Wanbin; Journal of Organometallic Chemistry; vol. 791; (2015); p. 41 - 45 View in Reaxys With D-glucose, glucose/glucose dehydrogenase, ene-reductase of the Old Yellow Enzyme 1, nicotinamide adenine dinucleotide phosphate in aq. phosphate buffer, dimethyl sulfoxide, T= 30 °C , pH= 7 Forchin, Maria Chiara; Crotti, Michele; Gatti, Francesco G.; Parmeggiani, Fabio; Brenna, Elisabetta; Monti, Daniela; ChemBioChem; vol. 16; nb. 11; (2015); p. 1571 - 1573 View in Reaxys O

O O

Rx-ID: 1553460 View in Reaxys 21/375 Yield 97 %

Conditions & References With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, water, sodium formate, (R,R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, T= 28 °C , Inert atmosphere Tang, Yuanfu; Xiang, Jing; Cun, Linfeng; Wang, Yuqin; Zhu, Jin; Liao, Jian; Deng, Jingen; Tetrahedron Asymmetry; vol. 21; nb. 15; (2010); p. 1900 - 1905 View in Reaxys

94.1 %

With Candida albicans, medium for yeast, Time= 72h, T= 30 °C , analogous reaction with other yeasts or with bacteria (at 37 deg C), Product distribution Mori; Ishiyama; Akita; Suzuki; Mitsuoka; Oishi; Chemical and Pharmaceutical Bulletin; vol. 38; nb. 12; (1990); p. 3449 - 3451 View in Reaxys

93 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.75h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

87 %

82 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys

81 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

80 %

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View in Reaxys 79 %

in water, Time= 120h, T= 24 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

77 %

With borohydride Ultra resin in methanol, Time= 2h, T= 20 °C Barth, Michael; Shah, Syed Tasadaque Ali; Rademann, Joerg; Tetrahedron; vol. 60; nb. 39; (2004); p. 8703 8709 View in Reaxys

70 %

With sodium cyanoborohydride, zeolite H-ZSM5 in methanol, Time= 3h, pH 6.5 Gupta, Anuradha; Haque, Azizul; Vankar, Yashwant D.; Chemical Communications; nb. 14; (1996); p. 1653 1654 View in Reaxys With C=C reductase from baker's yeast, NADPH, T= 35 °C Kawai, Yasushi; Hayashi, Motoko; Inaba, Yoshikazu; Saitou, Kentarou; Ohno, Atsuyoshi; Tetrahedron Letters; vol. 39; nb. 29; (1998); p. 5225 - 5228 View in Reaxys With sodium tetrahydroborate in tetrahydrofuran, methanol, T= 20 °C Fryszkowska, Anna; Fisher, Karl; Gardiner, John M.; Stephens, Gill M.; Journal of Organic Chemistry; vol. 73; nb. 11; (2008); p. 4295 - 4298 View in Reaxys With glucose dehydrogenase, D-glucose, xenobiotic reductase A C25G mutant, NADPH, pH= 7.5, aq. phosphate buffer Yanto, Yanto; Yu, Hua-Hsiang; Hall, Melanie; Bommarius, Andreas S.; Chemical Communications; vol. 46; nb. 46; (2010); p. 8809 - 8811 View in Reaxys With xenobiotic reductase B from Pseudomonas putida JLR11, NADH in dimethyl sulfoxide, Time= 24h, T= 30 °C , pH= 7.5, aq. buffer, Enzymatic reaction Durchschein, Katharina; Fabian, Walter M. F.; MacHeroux, Peter; Zangger, Klaus; Trimmel, Gregor; Faber, Kurt; Organic and Biomolecular Chemistry; vol. 9; nb. 9; (2011); p. 3364 - 3369 View in Reaxys With D-glucose, ene-reductase KYE1 from genomic DNA of Kluyveromyces lactis ATCC 8585, nicotinamide adenine dinucleotide phosphate, Time= 12h, T= 20 °C , pH= 7.5, aq. phosphate buffer, Enzymatic reaction Yanto, Yanto; Winkler, Christoph K.; Lohr, Stephanie; Hall, Melanie; Faber, Kurt; Bommarius, Andreas S.; Organic Letters; vol. 13; nb. 10; (2011); p. 2540 - 2543 View in Reaxys

92 %Chromat.

With glucose-6-phosphate dehydrogenase, D-glucose 6-phosphate, pentaerythritol tetranitrate reductase T26S mutant, NADPH in N,N-dimethyl-formamide, Time= 48h, T= 30 °C , pH= 7, aq. phosphate buffer, Enzymatic reaction Hulley, Martyn E.; Toogood, Helen S.; Fryszkowska, Anna; Mansell, David; Stephens, Gill M.; Gardiner, John M.; Scrutton, Nigel S.; ChemBioChem; vol. 11; nb. 17; (2010); p. 2433 - 2447 View in Reaxys

93 %Chromat.

With glucose-6-phosphate dehydrogenase, G-6-P, wild type pentaerythritol tetranitrate reductase, NADPH in N,Ndimethyl-formamide, Time= 48h, T= 30 °C , phosphate buffer, Inert atmosphere, anaerobic, Enzymatic reaction, enantioselective reaction Toogood, Helen S.; Fryszkowska, Anna; Hulley, Martyn; Sakuma, Michiyo; Mansell, David; Stephens, Gill M.; Gardiner, John M.; Scrutton, Nigel S.; ChemBioChem; vol. 12; nb. 5; (2011); p. 738 - 749 View in Reaxys

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With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys 2.5 Bioreduction of activated alkenes and product analysis General procedure: The bioreduction of various substrates was performed in 1-ml reaction system containing 100mM potassium phosphate buffer (pH 7.0), 10mM NADH, 5mM substrate, and 50μg purified Chr-OYE1 or 500μg purified Chr-OYE2. After 2-min or 16-h incubation at 30°C for Chr-OYE1 and Chr-OYE2, respectively, the reactions were terminated by extraction with ethyl acetate. The organic phase was analyzed using GC or HPLC. (0013) Preparative-scale biotransformation was performed in 30-ml reaction system for substrates 4a, 6a, and 12a–17a catalyzed with Chr-OYE1. The incubation was continued for 12h. The extracted organic phase was combined and concentrated under reduced pressure. The final product was purified with column chromatography and subjected to GC or HPLC analysis, as well as NMR analysis to confirm the structure and purity. With Chr-OYE1 (old yellow enzyme from chryseobacterium sp. CA49), β-nicotinamide adenine dinucleotide, oxidized form in aq. phosphate buffer, Time= 0.0333333h, T= 30 °C , pH= 7.0, Enzymatic reaction Pei, Xiao-Qiong; Xu, Meng-Yu; Wu, Zhong-Liu; Journal of Molecular Catalysis B: Enzymatic; vol. 123; (2016); p. 91 - 99 View in Reaxys O O

O N

O H

Rx-ID: 1986973 View in Reaxys 22/375 Yield

Conditions & References in water, Time= 48h, T= 30 °C , microbial reduction with Rhodococcus rhodochrous IFO 3338, Yield given. Yields of byproduct given. Title compound not separated from byproducts Sakai, Kunikazu; Nakazawa, Akiko; Kondo, Kiyoshi; Ohta, Hiromichi; Agricultural and Biological Chemistry; vol. 49; nb. 8; (1985); p. 2331 - 2336 View in Reaxys in water, Time= 48h, T= 30 °C , microbial reduction with Rhodococcus rhodochrous IFO 3338, Yield given. Yields of byproduct given Sakai, Kunikazu; Nakazawa, Akiko; Kondo, Kiyoshi; Ohta, Hiromichi; Agricultural and Biological Chemistry; vol. 49; nb. 8; (1985); p. 2331 - 2336 View in Reaxys

O N

N O

Rx-ID: 1987253 View in Reaxys 23/375 Yield 97 %

Conditions & References 4.2. Typical procedure for the reduction of conjugated nitroalkenes General procedure: The mixture of nitroalkenes 1 (0.1 g, 0.67 mmol), Hantzsch ester (0.19 g, 0.74 mmol) and Sbenzyl isothiouronium chloride (14 mg, 0.067 mmol) in methanol (5 ml) was stirred at 60 °C for 5-12 h. After completion of the reaction, the crude product in methanol was concentrated and added into the excess cooled CH2Cl2. The S-benzyl isothiouronium chloride was readily precipitated out, and then filtered and washed many times with CH2Cl2 to be reused. The filtrate was evaporated and the residue was purified by flash column chromatography to give the required nitroalkanes products 2. All nitroalkanes except 2j and 2p were characterized with the reported spectroscopic data. [2] and [5] With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, S-benzyl isothiouronium chloride in methanol, T= 60 °C , Inert atmosphere Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron; vol. 68; nb. 32; (2012); p. 6513 6516

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View in Reaxys 95 %

94 %

90 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.25h Ballini, Roberto; Petrini, Marino; Marotta, Emanuela; Synthetic Communications; vol. 17; nb. 5; (1987); p. 543 548 View in Reaxys

86 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 4h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

85 %

With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, Time= 3h, Heating Chikashita, Hidenori; Morita, Yasuhiro; Itoh, Kazuyoshi; Synthetic Communications; vol. 15; nb. 6; (1985); p. 527 - 534 View in Reaxys

85 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 4h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

80 %

With nickel(II) ferrite, isopropyl alcohol, Time= 3h, T= 80 °C , Green chemistry Payra, Soumen; Saha, Arijit; Banerjee, Subhash; RSC Advances; vol. 6; nb. 57; (2016); p. 52495 - 52499 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1) methylene chloride, room temp., 20h, 2) methanol, -15 deg C, Yield given. Multistep reaction Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys

2.62 g

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Rx-ID: 2141836 View in Reaxys 24/375 Yield

Conditions & References

73 %

in water, Time= 73h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Rx-ID: 2152664 View in Reaxys 25/375 Yield

Conditions & References

80 %

76 %

67 %

in water, Time= 72h, T= 32 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Rx-ID: 3249543 View in Reaxys 26/375 Yield

Conditions & References

41 %

in water, Time= 72h, T= 32 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Z N

O O

N O

Rx-ID: 3961122 View in Reaxys 27/375 Yield 85 %

Conditions & References With PBI in butan-1-ol, Time= 3h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

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O Z

O O

Rx-ID: 3964422 View in Reaxys 28/375 Yield

Conditions & References

91 %

With PBI in butan-1-ol, Time= 6h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

O O

LiAlH4

O O

H N

H 2N

1-phenyl-propanone oxime

Rx-ID: 6681954 View in Reaxys 29/375 Yield

Conditions & References Product distribution Gilsdorf; Nord; Journal of the American Chemical Society; vol. 74; (1952); p. 1837,1841 View in Reaxys

O O

O E

Rx-ID: 9178685 View in Reaxys 30/375 Yield

Conditions & References With tris(triphenylphosphine)ruthenium(II) chloride, hydrogen in dichloromethane, Time= 24h, p= 14710.2Torr , Heating Li, Yanjun; Izumi, Taeko; Journal of the Chinese Chemical Society (Taipei, Taiwan); vol. 49; nb. 4; (2002); p. 505 508 View in Reaxys With glycerol trinitrate reductase from Agrobacterium radiobacter, Reduced nicotinamide-adenine dinucleotide in dimethyl sulfoxide, Time= 24h, T= 30 °C , pH= 7.5, aq. buffer, Enzymatic reaction Durchschein, Katharina; Fabian, Walter M. F.; MacHeroux, Peter; Zangger, Klaus; Trimmel, Gregor; Faber, Kurt; Organic and Biomolecular Chemistry; vol. 9; nb. 9; (2011); p. 3364 - 3369 View in Reaxys

O O

O N

O H

Rx-ID: 27925380 View in Reaxys 31/375 Yield , 27.7 %

Conditions & References With bis(norbornadiene)rhodium(l)tetrafluoroborate, hydrogen, (R,R)-1,2-bis(2,5-diphenylphospholanyl)ethane in dichloromethane, Time= 24h, T= 50 °C , p= 60804.1Torr , Autoclave, Reagent/catalyst, enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

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With 1,4-dihydronicotinamide adenine dinucleotide, hydrogen in phosphate buffer, 2,2,4-trimethylpentane, T= 30 °C , pH= 7.0, Title compound not separated from byproducts. Fryszkowska, Anna; Fisher, Karl; Gardiner, John M.; Stephens, Gill M.; Journal of Organic Chemistry; vol. 73; nb. 11; (2008); p. 4295 - 4298 View in Reaxys O O

O N

O H

Rx-ID: 28714426 View in Reaxys 32/375 Yield

Conditions & References With glucose-6-phosphate, pentaerythritol tetranitrate reductase, NADP+, glucose 6-phosphate dehydrogenase in 2,2,4-trimethylpentane, sec-Butylbenzene, Time= 72h, T= 30 °C , pH= 7, aq. phosphate buffer, Inert atmosphere, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction Toogood, Helen S.; Fryszkowska, Anna; Hare, Victoria; Fisher, Karl; Roujeinikova, Anna; Leys, David; Gardiner, John M.; Stephens, Gill M.; Scrutton, Nigel S.; Advanced Synthesis and Catalysis; vol. 350; nb. 17; (2008); p. 2789 - 2803 View in Reaxys With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Catalytic behavior, Reagent/catalyst, Temperature, Time, Pressure, Overall yield = 92 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O O

Rx-ID: 29629445 View in Reaxys 33/375 Yield

Conditions & References

41 %, 10 %

With palladium 10 on activated carbon, hydrogen in methanol, Time= 0.666667h, T= 20 °C Durchschein, Katharina; Ferreira-Da Silva, Bianca; Wallner, Silvia; MacHeroux, Peter; Kroutil, Wolfgang; Glueck, Silvia Maria; Faber, Kurt; Green Chemistry; vol. 12; nb. 4; (2010); p. 616 - 619 View in Reaxys

O O

O E

Rx-ID: 32288948 View in Reaxys 34/375 Yield

Conditions & References With glucose-6-phosphate dehydrogenase, G-6-P, wild type pentaerythritol tetranitrate reductase, NADPH in N,Ndimethyl-formamide, Time= 4h, T= 30 °C , phosphate buffer, Inert atmosphere, anaerobic, Enzymatic reaction, enantioselective reaction Toogood, Helen S.; Fryszkowska, Anna; Hulley, Martyn; Sakuma, Michiyo; Mansell, David; Stephens, Gill M.; Gardiner, John M.; Scrutton, Nigel S.; ChemBioChem; vol. 12; nb. 5; (2011); p. 738 - 749 View in Reaxys

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O O

O H

Rx-ID: 36298029 View in Reaxys 35/375 Yield

Conditions & References With glucose dehydrogenase, D-Glucose, NADPH, citric acid in aq. phosphate buffer, ethanol, Time= 10h, T= 9 °C , pH= 6, Sonication, enantioselective reaction Burda, Edyta; Reß, Tina; Winkler, Till; Giese, Carolin; Kostrov, Xenia; Huber, Tobias; Hummel, Werner; Gröger, Harald; Angewandte Chemie - International Edition; vol. 52; nb. 35; (2013); p. 9323 - 9326; Angew. Chem.; vol. 125; nb. 35; (2013); p. 9493 - 9496 View in Reaxys O

O O

NH 2

Rx-ID: 11123784 View in Reaxys 36/375 Yield

Conditions & References

60 % Chromat., 2 % Chromat., 23 % Chromat., 8 % Chromat.

O O

With hydrogen, palladium on activated charcoal, Time= 0.25h, T= 110 °C , p= 11251.1Torr , Product distribution, Further Variations: Catalysts Corma, Avelino; Serna, Pedro; Garcia, Hermenegildo; Journal of the American Chemical Society; vol. 129; nb. 20; (2007); p. 6358 - 6359 View in Reaxys

O O

NH 2

Rx-ID: 15502718 View in Reaxys 37/375 Yield

Conditions & References Reaction Steps: 2 1: 75 percent / NaBH4 / methanol / 0.75 h / 20 °C 2: 83 percent / 1,1'-dioctyl-4,4'-bipyridinium dibromide; Sm / methanol / 5 h / 20 °C With samarium, sodium tetrahydroborate, 1,1'-di-n-octyl-4,4'-bipyridinium dibromide in methanol Yu; Liu; Hu; Journal of Organic Chemistry; vol. 66; nb. 3; (2001); p. 919 - 924 View in Reaxys Reaction Steps: 2 1: sodium tetrahydroborate / methanol / 1.5 h / 20 °C / |Inert atmosphere 2: 10 Pd/C; hydrogen / methanol / |Inert atmosphere With sodium tetrahydroborate, 10 Pd/C, hydrogen in methanol Anderson, James C.; Noble, Adam; Torres, Pascual Ribelles; Tetrahedron Letters; vol. 53; nb. 42; (2012); p. 5707 - 5710 View in Reaxys Reaction Steps: 2 1: diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate / neat (no solvent) / 100 °C 2: hydrogen; palladium on activated charcoal / methanol With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, palladium on activated charcoal, hydrogen in methanol Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831

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View in Reaxys

NH 2

NH 2 N

Rx-ID: 33914439 View in Reaxys 38/375 Yield

Conditions & References With potassium borohydride in ethanol, T= 5 °C Zhou, Li-Yi; Yang, Jun; Yan, Xi-Qing; Pan, Yan-Juan; Wu, Feng; Zhang, Jing; Yan, Fu-Lin; Lu, Guang-Zhou; Asian Journal of Chemistry; vol. 24; nb. 4; (2012); p. 1538 - 1540 View in Reaxys

O N O

Rx-ID: 4814683 View in Reaxys 39/375 Yield

Conditions & References

57 %

With sodium borodeuteride in dichloromethane, isopropyl alcohol McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys With [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], water, sodium lt;1-(2)Hgt;formate, (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, T= 28 °C , Inert atmosphere Tang, Yuanfu; Xiang, Jing; Cun, Linfeng; Wang, Yuqin; Zhu, Jin; Liao, Jian; Deng, Jingen; Tetrahedron Asymmetry; vol. 21; nb. 15; (2010); p. 1900 - 1905 View in Reaxys

O N

Rx-ID: 4823512 View in Reaxys 40/375 Yield

Conditions & References

73 %

O O

N O

Rx-ID: 29820274 View in Reaxys 41/375 Yield

Conditions & References With [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], water-d2, sodium formate, (1R,2R)-N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine, T= 28 °C , Inert atmosphere Tang, Yuanfu; Xiang, Jing; Cun, Linfeng; Wang, Yuqin; Zhu, Jin; Liao, Jian; Deng, Jingen; Tetrahedron Asymmetry; vol. 21; nb. 15; (2010); p. 1900 - 1905 View in Reaxys

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OH N

Rx-ID: 2067571 View in Reaxys 42/375 Yield

Conditions & References

96 %

91 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

78 %

With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, Time= 6h, Heating Chikashita, Hidenori; Morita, Yasuhiro; Itoh, Kazuyoshi; Synthetic Communications; vol. 15; nb. 6; (1985); p. 527 - 534 View in Reaxys With sodium tetrahydroborate in ethanol Iida; Kikuchi; Kobayashi; Ina; Tetrahedron Letters; vol. 21; nb. 8; (1980); p. 759 - 760 View in Reaxys

O O

OH E

O O

Rx-ID: 2194459 View in Reaxys 43/375 Yield 83 %

Conditions & References With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, T= 20 °C Zhang, Bang-Le; Wang, Fang-Dao; Yue, Jian-Min; Synlett; nb. 4; (2006); p. 567 - 570 View in Reaxys

83 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 1h

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Fuganti, Claudio; Sacchetti, Alessandro; Journal of Molecular Catalysis B: Enzymatic; vol. 66; nb. 3-4; (2010); p. 276 - 284 View in Reaxys 76 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1h, T= 0 °C Yang, Fanzhi; Rauch, Karsten; Kettelhoit, Katharina; Ackermann, Lutz; Angewandte Chemie - International Edition; vol. 53; nb. 42; (2014); p. 11285 - 11288; Angew. Chem.; vol. 126; nb. 42; (2014); p. 11467 - 11470,4 View in Reaxys

OH N

Rx-ID: 2198783 View in Reaxys 44/375 Yield

Conditions & References

75 %

37 %

in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys With sodium tetrahydroborate in ethanol, Time= 24h, Ambient temperature Ina, Hiroji; Iida, Hideo; Chemical and Pharmaceutical Bulletin; vol. 34; (1986); p. 726 - 729 View in Reaxys

Z N

OH N

Rx-ID: 3964655 View in Reaxys 45/375 Yield 78 %

Conditions & References With PBI in butan-1-ol, Time= 6h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

O O

Rx-ID: 32246543 View in Reaxys 46/375 Yield 82 %

Conditions & References With methanol, sodium tetrahydroborate, Time= 0.5h, T= 0 °C Zheng, Purong; Somersan-Karakaya, Selin; Lu, Shichao; Roberts, Julia; Pingle, Maneesh; Warrier, Thulasi; Little, David; Guo, Xiaoyong; Brickner, Steven J.; Nathan, Carl F.; Gold, Ben; Liu, Gang; Journal of Medicinal Chemistry; vol. 57; nb. 9; (2014); p. 3755 - 3772 View in Reaxys With sodium tetrahydroborate in tetrahydrofuran, methanol, T= 0 - 20 °C , Inert atmosphere

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Hoveyda, Hamid R.; Marsault, Eric; Gagnon, Rene; Mathieu, Axel P.; Vezina, Martin; Landry, Annick; Wang, Zhigang; Benakli, Kamel; Beaubien, Sylvie; Saint-Louis, Carl; Brassard, Martin; Pinault, Jean-Francois; Ouellet, Luc; Bhat, Shridhar; Ramaseshan, Mahesh; Peng, Xiaowen; Foucher, Laurence; Beauchemin, Sophie; Bherer, Patrick; Veber, Daniel F.; Peterson, Mark L.; Fraser, Graeme L.; Journal of Medicinal Chemistry; vol. 54; nb. 24; (2011); p. 8305 - 8320 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys O

Rx-ID: 34846046 View in Reaxys 47/375 Yield

Conditions & References

56.4 %

To a cold (0 °C) solution of Intermediate BS (350mg, 2.12 mmol) in methanol (3.5 mL) at 0 °C was added portionwise NaBH4 (1 OOmg, 2.54 mmol) over 5 minutes. After the addition was complete, the reaction mixture was allowed to stir at 10 °C for 1 hour. The reaction mixture was quenched with water (5 mL) and concentrated under reduced pressure. The resulting aqueous residue was diluted with water (15 mL) and extracted with ethyl acetate (2 χ 20 mL). The combined ethyl acetate layers were washed with water (10 mL) and brine solution (15 mL), dried over anhydrous Na2S04, and the solvent was removed to afford the crude product. This material was purified by column chromatography (silica gel 100-200 mesh) using 10percent ethyl acetate in petroleum ether as the eluent to afford Intermediate BT (200 mg, 56.4percent) as a pale yellow solid. NMR (CDC13): δ 7.19 (s, J = 7.90 Hz; 1H), 6.77-6.72 (m, 2H), 6.68 (s, 1H), 4.59 (t, J= 7.32 Hz, 2H), 3.27 (t, J = 7.32 Hz). Mass (M-H): 166.0. With sodium tetrahydroborate in methanol, Time= 1.25h, T= 0 - 10 °C Patent; HERCULES TECHNOLOGY MANAGEMENT CO V, INC.; BLAGG, Julian; WO2011/47156; (2011); (A1) English View in Reaxys

N 2H

Rx-ID: 4823511 View in Reaxys 48/375 Yield

Conditions & References With Mauripan Instant Dry Yeast, water-d2 in Petroleum ether, Time= 24h, Ambient temperature, Title compound not separated from byproducts McAnda, Anita F.; Roberts, Kade D.; Smallridge, Andrew J.; Ten, Abilio; Trewhella, Maurie A.; Journal of the Chemical Society - Perkin Transactions 1; nb. 3; (1998); p. 501 - 504 View in Reaxys O

O N

Rx-ID: 29831112 View in Reaxys 49/375 Yield 93 %

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 1h Fuganti, Claudio; Sacchetti, Alessandro; Journal of Molecular Catalysis B: Enzymatic; vol. 66; nb. 3-4; (2010); p. 276 - 284 View in Reaxys

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N O

Rx-ID: 29961056 View in Reaxys 50/375 Yield 96 %

Conditions & References With 1,4-diaza-bicyclo[2.2.2]octane, tris(2,4,6-trifluorophenyl)borane triethylphosphine oxide, Time= 24h, T= 50 °C , p= 3750.38Torr , Inert atmosphere Nicasio, Juan A.; Steinberg, Sebastian; Ines, Blanca; Alcarazo, Manuel; Chemistry - A European Journal; vol. 19; nb. 33; (2013); p. 11016 - 11020 View in Reaxys

95 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 1.5h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

95 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

85 %

4.1.3. General procedure A: preparation of 1-aryl-1-nitroethanes General procedure: Sodium borohydride (15.00 mmol, 5.70 g) was added to a vigorously stirred mixture of the appropriate nitroethene (3.68 mmol), silica gel (9.30 g) and propan-2-ol (100 mL) in dichloromethane (350 mL) at room temperature. The mixture was stirred at room temperature for 20 min until the solution turned colourless. Excess NaBH4 was quenched with the addition of dilute HCl (50 mL). The mixture was filtered and the silica gel washed with dichloromethane (100 mL). All organic phases were combined and washed with brine (3 .x. 50 mL) and water (3 .x. 50 mL). The organic phases were then dried over anhydrous Mg2SO4 and the solvent removed in vacuo. The crude product was purified by column chromatography over silica gel. With sodium tetrahydroborate, silica gel in dichloromethane, isopropyl alcohol, Time= 0.333333h, T= 20 °C McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Guenther H.; Meegan, Mary J.; Williams, D. Clive; Bioorganic and Medicinal Chemistry; vol. 19; nb. 3; (2011); p. 1328 - 1348 View in Reaxys With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, T= 20 °C , Inert atmosphere, Reflux Zhang, Fanglin; Wei, Mohui; Dong, Junfang; Zhou, Yirong; Lu, Dengfu; Gong, Yuefa; Yang, Xiangliang; Advanced Synthesis and Catalysis; vol. 352; nb. 17; (2010); p. 2875 - 2880 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhao, Xinyang; Wang, Xinbo; Liu, Qisong; Li, Zigang; Wang, David Zhigang; Angewandte Chemie - International Edition; vol. 51; nb. 32; (2012); p. 8050 - 8053 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere

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Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

N N

Rx-ID: 2069359 View in Reaxys 51/375 Yield

Conditions & References

96 %

95 %

4.2. Typical procedure for the reduction of conjugated nitroalkenes General procedure: The mixture of nitroalkenes 1 (0.1 g, 0.67 mmol), Hantzsch ester (0.19 g, 0.74 mmol) and Sbenzyl isothiouronium chloride (14 mg, 0.067 mmol) in methanol (5 ml) was stirred at 60 °C for 5-12 h. After completion of the reaction, the crude product in methanol was concentrated and added into the excess cooled CH2Cl2. The S-benzyl isothiouronium chloride was readily precipitated out, and then filtered and washed many times with CH2Cl2 to be reused. The filtrate was evaporated and the residue was purified by flash column chromatography to give the required nitroalkanes products 2. All nitroalkanes except 2j and 2p were characterized with the reported spectroscopic data. [2] and [5] With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, S-benzyl isothiouronium chloride in methanol, T= 60 °C , Inert atmosphere Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron; vol. 68; nb. 32; (2012); p. 6513 6516 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1) methylene chloride, room temp., 15h, 2) methanol, -15 deg C, Yield given. Multistep reaction Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

O N

N N

Rx-ID: 2069364 View in Reaxys 52/375 Yield 28 %

Conditions & References in water, Time= 74h, T= 31 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

12 %

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O N

N E

Rx-ID: 2194434 View in Reaxys 53/375 Yield 69 %

Conditions & References in water, Time= 73h, T= 31 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys O

O N

Rx-ID: 309290 View in Reaxys 54/375 Yield

Conditions & References With palladium on activated charcoal, water Patent; Comm. Solv. Corp.; US2483201; (1945) View in Reaxys With formic acid, triethylamine in N,N-dimethyl-formamide Nanjo,K.; Sekija,M.; Chemical and Pharmaceutical Bulletin; vol. 27; (1979); p. 198 - 203 View in Reaxys

O N

Rx-ID: 1104241 View in Reaxys 55/375 Yield 99 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 3h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys With sodium tetrahydroborate Bailey,K. et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 3143 - 3151 View in Reaxys

O O

Rx-ID: 1121103 View in Reaxys 56/375 Yield

Conditions & References With sodium tetrahydroborate

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Bailey,K. et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 3143 - 3151 View in Reaxys O O

Rx-ID: 1194787 View in Reaxys 57/375 Yield

Conditions & References

87 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys With sodium tetrahydroborate Bailey,K. et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 3143 - 3151 View in Reaxys

O N

Rx-ID: 2766247 View in Reaxys 58/375 Yield

Conditions & References

80 %

61 %

in water, Time= 71h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

58 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O O

O E

Rx-ID: 3212310 View in Reaxys 59/375

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Yield

Conditions & References

61 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

59 %

in water, Time= 48h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys O Z

Rx-ID: 3226398 View in Reaxys 60/375 Yield

Conditions & References With sodium tetrahydroborate in ethanol Striegel; Mayer; Wiegrebe; Schlunegger; Siegrist; Aebi; Archiv der Pharmazie; vol. 325; nb. 12; (1992); p. 751 760 View in Reaxys

O O

Rx-ID: 3226399 View in Reaxys 61/375 Yield

Conditions & References

69 %

in water, Time= 71h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

65 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys O Z

Rx-ID: 3964471 View in Reaxys 62/375 Yield

Conditions & References

87 %

With PBI in butan-1-ol, Time= 8h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

O O

O E

Rx-ID: 8813419 View in Reaxys 63/375 Yield 58 %

Conditions & References With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318

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View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys O

O N

(-)-enantiomer,rel-configuration

(+)-enantiomer,rel-configuration

Rx-ID: 38266811 View in Reaxys 64/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 41percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O N

(+)-enantiomer,rel-configuration

(-)-enantiomer,rel-configuration

Rx-ID: 38266875 View in Reaxys 65/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 73 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

N O

O N

Rx-ID: 1074697 View in Reaxys 66/375 Yield 99 %

Conditions & References With acetic acid in N,N-dimethyl-formamide, Time= 0.333333h, T= 150 °C , Microwave irradiation, chemoselective reaction Che, Jun; Lam, Yulin; Advanced Synthesis and Catalysis; vol. 352; nb. 10; (2010); p. 1752 - 1758 View in Reaxys

93 %

90 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 - 5 °C Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

90 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 °C

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Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys 90 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

87 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 5h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

77 %

With magnesium(II) perchlorate, "grafted NADH model" reagent in acetonitrile, benzene, Time= 120h, T= 80 °C Trefouel, Thierry; Tintillier, Patrik; Dupas, Georges; Bourguignon, Jean; Queguiner, Guy; Bulletin of the Chemical Society of Japan; vol. 60; nb. 12; (1987); p. 4492 - 4494 View in Reaxys With Wilkinson's catalyst, hydrogen Birch,A.J.; Walker,K.A.M.; Australian Journal of Chemistry; vol. 24; (1971); p. 513 - 520 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1) methylene chloride, room temp., 20h, 2) methanol, -15 deg C, Yield given. Multistep reaction Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1.) methylene chloride, 20-24h, room temperature; 2.) MeOH, methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys

95 % Chromat.

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With 2,6-dimethylpyridine, C18H9BF6*C4H8O, hydrogen in dichloromethane-d2, Time= 24h, T= -196.16 - 40 °C , p= 3000.3Torr , Inert atmosphere, Schlenk technique, Glovebox Greb, Lutz; Daniliuc, Constantin-Gabriel; Bergander, Klaus; Paradies, Jan; Angewandte Chemie - International Edition; vol. 52; nb. 22; (2013); p. 5876 - 5879; Angew. Chem.; vol. 125; nb. 22; (2013); p. 5989 - 5992,4 View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol Rezazadeh, Sina; Devannah, Vijayarajan; Watson, Donald A.; Journal of the American Chemical Society; vol. 139; nb. 24; (2017); p. 8110 - 8113 View in Reaxys

O N

N O

O H

Rx-ID: 1986970 View in Reaxys 67/375 Yield

Conditions & References in water, Time= 48h, T= 30 °C , microbial reduction with Rhodococcus rhodochrous IFO 3338; other pH, other microoranism, Product distribution Sakai, Kunikazu; Nakazawa, Akiko; Kondo, Kiyoshi; Ohta, Hiromichi; Agricultural and Biological Chemistry; vol. 49; nb. 8; (1985); p. 2331 - 2336 View in Reaxys

O N

Rx-ID: 2071009 View in Reaxys 68/375 Yield

Conditions & References

10 %

With tri-n-butyl-tin hydride, ozone, 1.) methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys

O N

Rx-ID: 2071045 View in Reaxys 69/375 Yield 94 %

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.416667h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230

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View in Reaxys 90 %

85%

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

85 %

With nickel(II) ferrite, isopropyl alcohol, Time= 3h, T= 80 °C , Green chemistry Payra, Soumen; Saha, Arijit; Banerjee, Subhash; RSC Advances; vol. 6; nb. 57; (2016); p. 52495 - 52499 View in Reaxys

84 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys

82 %

81 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 1h Fuganti, Claudio; Sacchetti, Alessandro; Journal of Molecular Catalysis B: Enzymatic; vol. 66; nb. 3-4; (2010); p. 276 - 284 View in Reaxys

75 %

in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

74 %

1-Methoxy-4-(2-nitroethyl)benzene 2d To efficiently stirred suspension of well-dispersed sodium borohydride (836 mg, 22 mmol) in dioxane (20 mL) and ethanol (5 mL) mixture was added (E)-p-methyxy-β-nitrostyrene (1.79 g, 10 mmol) in dioxane (20 mL) over period of 15 minutes while maintaining temperature below 25 °C (water bath). After the addition was completed, the reaction mixture was stirred for 1 hour and the resultant slurry was diluted with ice water (30mL). The excess boron hydride was quenched with glacial acetic acid (water bath cooling remaining). The solution was poured into EtOAc (200 mL)/ water (50 mL) mixture, organic phase was separated out and the aqueous one was back-extracted with EtOAc (2×50 mL). Combined organic layers were washed with water(100 mL) and brine (200 mL), dried with Na2SO4 and concentrated on rotary evaporator. The crude product was purified by column chromatography on silica (eluent EtOAc/hexane, 1/10) to give β-arylnitroethane 2d (1.34 g,7.4 mmol, 74percent) as yellow oil. With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.25h, T= 25 °C Mikhaylov, Andrey A.; Dilman, Alexander D.; Novikov, Roman A.; Khoroshutina, Yulia A.; Struchkova, Marina I.; Arkhipov, Dmitry E.; Nelyubina, Yulia V.; Tabolin, Andrey A.; Ioffe, Sema L.; Tetrahedron Letters; vol. 57; nb. 1; (2016); p. 11 - 14 View in Reaxys

72 %

65 %

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View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.25h, T= 25 °C Kodukulla; Trivedi; Vora; Mathur; Synthetic Communications; vol. 24; nb. 6; (1994); p. 819 - 832 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhao, Xinyang; Wang, Xinbo; Liu, Qisong; Li, Zigang; Wang, David Zhigang; Angewandte Chemie - International Edition; vol. 51; nb. 32; (2012); p. 8050 - 8053 View in Reaxys O O

O O

Rx-ID: 2088678 View in Reaxys 70/375 Yield 96 %

Conditions & References With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, acetic acid in benzene, Time= 15h, T= 80 °C Inoue, Yoshio; Imaizumi, Shin; Itoh, Hiromitsu; Shinya, Takao; Hashimoto, Harukichi; Miyano, Sotaro; Bulletin of the Chemical Society of Japan; vol. 61; (1988); p. 3020 - 3022 View in Reaxys

95 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, Ambient temperature Ambros, Reinhard; Schneider, Martin R.; Angerer, Silvia von; Journal of Medicinal Chemistry; vol. 33; nb. 1; (1990); p. 153 - 160 View in Reaxys

93 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 - 5 °C Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

93 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 °C Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys

88 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

71 %

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required nitroalkanes products 2. All nitroalkanes except 2j and 2p were characterized with the reported spectroscopic data. [2] and [5] With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, S-benzyl isothiouronium chloride in methanol, T= 60 °C , Inert atmosphere Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron; vol. 68; nb. 32; (2012); p. 6513 6516 View in Reaxys

O O

Rx-ID: 2089537 View in Reaxys 71/375 Yield

Conditions & References

94 %

With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, silica gel in benzene, Time= 20h, T= 60 °C Nakamura, Kaoru; Fujii, Masayuki; Oka, Shinzaburo; Ohno, Atsuyoshi; Chemistry Letters; (1985); p. 523 - 526 View in Reaxys

92 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.833333h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

88 %

85 %

84 %

With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, silica gel in benzene, Time= 0.5h, Heating FUJI, Masayuki; Bulletin of the Chemical Society of Japan; vol. 61; nb. 11; (1988); p. 4029 - 4036 View in Reaxys

57 %

in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

O O

O E

Rx-ID: 2117869 View in Reaxys 72/375 Yield 81 %

Conditions & References in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

39/143

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HO N

Rx-ID: 2153006 View in Reaxys 73/375 Yield

Conditions & References in water, Time= 48h, T= 30 °C , microbial reduction with Rhodococcus rhodochrous IFO 3338; other microorganism, other pH, Product distribution Sakai, Kunikazu; Nakazawa, Akiko; Kondo, Kiyoshi; Ohta, Hiromichi; Agricultural and Biological Chemistry; vol. 49; nb. 8; (1985); p. 2331 - 2336 View in Reaxys in water, Time= 48h, T= 30 °C , microbial reduction with Rhodococcus rhodochrous IFO 3338, Yield given. Yields of byproduct given. Title compound not separated from byproducts Sakai, Kunikazu; Nakazawa, Akiko; Kondo, Kiyoshi; Ohta, Hiromichi; Agricultural and Biological Chemistry; vol. 49; nb. 8; (1985); p. 2331 - 2336 View in Reaxys in water, Time= 48h, T= 30 °C , microbial reduction with Rhodococcus rhodochrous IFO 3338, Yields of byproduct given. Title compound not separated from byproducts Sakai, Kunikazu; Nakazawa, Akiko; Kondo, Kiyoshi; Ohta, Hiromichi; Agricultural and Biological Chemistry; vol. 49; nb. 8; (1985); p. 2331 - 2336 View in Reaxys

OH N

Rx-ID: 2194551 View in Reaxys 74/375 Yield

Conditions & References

69 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Z N

O N

Rx-ID: 3964942 View in Reaxys 75/375 Yield

Conditions & References

93 %

With PBI in butan-1-ol, Time= 3h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

O N O

H 2N

O N

H 2N

Rx-ID: 24345586 View in Reaxys 76/375 Yield 93%

Conditions & References 227 : Isomer B: (+-) (trans) 5-[(4-methoxyphenyl)methyl]-3-methylpyrrolidin-2-imine, monohydrochloride STR232 Isomer B: (+-) (trans) 5-[(4-methoxyphenyl)methyl]-3-methylpyrrolidin-2-imine, monohydrochloride STR232

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Example 227 A) 4-Methoxy-β-nitrostyrene (25.0 g, 0.15 mole) was reacted with benzaldehyde (19.1 g, 0.18 mole) and 1,2-diaminobenzene (19.8 g, 0.18 mole) according to the procedure of Chikashita et. al. (Synth. Commun. 1985, 15 (6), 527) to yield methoxy-4-(2-nitroethyl) benzene (25.0 g, 93percent) as a yellow oil. With benzaldehyde Patent; G.D. Searle and Co.; US6011028; (2000); (A1) English View in Reaxys O

Rx-ID: 24509685 View in Reaxys 77/375 Yield

Conditions & References 58 : Preparation 58 Preparation 58 A solution of (Z)-1-(3-methoxyphenyl)-2-nitroethene (33.85 g) in 1,4-dioxane (315 ml) was added dropwise to an efficiently stirred suspension of sodium borohydride (15.77 g) in a mixture of 1,4-dioxane (315 ml) and ethanol (98 ml) over a period of 0.5 hour while maintaining a temperature of 30° C. After stirring for 2 hours, the resultant slurry was diluted with ice water (393 ml) and the excess sodium borohydride was decomposed with 50percent aqueous acetic acid (47.4 ml). To the solution, sodium chloride (68 g) and ethyl acetate were added. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by distillation under reduced pressure to give 1-methoxy-3-(2-nitroethyl)benzene (23.62 g). bp: 104°-107° C./1 mmHg. IR (Neat): 1540, 1375 cm-1 NMR (CDCl3, δ): 3.29 (2H, t, J=7.4 Hz), 3.80 (3H, s), 4.60 (2H, t, J=7.4 Hz), 6.70-6.87 (3H, m), 7.19-7.33 (1H, m) With sodium borohydride, sodium chloride, acetic acid in 1,4-dioxane, ethanol, ethyl acetate Patent; Fujisawa Pharmaceutical Co., Ltd.; US5387710; (1995); (A1) English View in Reaxys

O O

Rx-ID: 30636177 View in Reaxys 78/375 Yield

Conditions & References Reaction Steps: 2 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: boron tribromide / chloroform / -78 - 20 °C / Inert atmosphere With sodium tetrahydroborate, boron tribromide, sodium hydroxide in ethanol, chloroform Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

O O

Rx-ID: 33493017 View in Reaxys 79/375 Yield 88 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes

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General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhao, Xinyang; Wang, Xinbo; Liu, Qisong; Li, Zigang; Wang, David Zhigang; Angewandte Chemie - International Edition; vol. 51; nb. 32; (2012); p. 8050 - 8053 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

OH N

Rx-ID: 33493019 View in Reaxys 80/375 Yield 75 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 12h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys OH

O N

O O

N O

Rx-ID: 44499373 View in Reaxys 81/375 Yield 64 %

Conditions & References With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.5h, T= 0 - 20 °C Wilsdorf; Schmidt; Bartetzko; Dallabernardina; Schuhmacher; Seeberger; Pfrengle; Chemical Communications; vol. 52; nb. 66; (2016); p. 10187 - 10189 View in Reaxys

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Rx-ID: 30636178 View in Reaxys 82/375 Yield

Conditions & References Reaction Steps: 3 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: pyridine; methanol-d4 / 35 h / Reflux; Inert atmosphere 3: boron tribromide / chloroform / -78 - 20 °C / Inert atmosphere With pyridine, sodium tetrahydroborate, methanol-d4, boron tribromide, sodium hydroxide in ethanol, chloroform Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

O N

Rx-ID: 2547133 View in Reaxys 83/375 Yield

Conditions & References

87 %

With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, Time= 0.666667h, T= 20 °C Zhang, Bang-Le; Wang, Fang-Dao; Yue, Jian-Min; Synlett; nb. 4; (2006); p. 567 - 570 View in Reaxys

70 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys O N

O N

Rx-ID: 29957876 View in Reaxys 84/375 Yield

Conditions & References With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, Time= 0.666667h, T= 20 °C , Inert atmosphere Zhang, Bang-Le; Fan, Cheng-Qi; Dong, Lei; Wang, Fang-Dao; Yue, Jian-Min; European Journal of Medicinal Chemistry; vol. 45; nb. 11; (2010); p. 5258 - 5264 View in Reaxys

Rx-ID: 30382065 View in Reaxys 85/375 Yield

Conditions & References 8.2 :Analogously to the procedure described in A. K. Sinhababu et al., Tetrahedron Lett. 24 (1983), 227, to a solution of the compound of step 1 (16.85 g, 93.01 mmol) in isopropanol (275 ml) and chloroform (825 ml) were added dry silica gel (110 g) and then in small portions sodium borohydhde (7.038 g, 186.02 mmol). The mixture was stirred at room temperature for 0.5 h, then cooled to 0 0C and quenched by slow addition of 10 ml of 5 N hydrochloric acid. After stirring for 10 min, the silica gel was filtered off and the filtrate was concentrated to dryness under reduced pressure. The residue was dissolved in 150 ml of DCM and the solution washed with water (75 ml) and brine (75 ml),

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dried over magnesium sulfate, filtered and evaporated to dryness to give 15.02 g of the title compound as a thick orange oil With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.5h, T= 20 °C Patent; SANOFI-AVENTIS; STEINHAGEN, Henning; SCHEIPER, Bodo; MATTER, Hans; MCCORT, Gary; BEGIS, Guillaume; GOBERVILLE, Pascale; THIERS, Berangere; WO2011/12538; (2011); (A1) English View in Reaxys

F N

Rx-ID: 33493018 View in Reaxys 86/375 Yield

Conditions & References

85 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

Rx-ID: 33493020 View in Reaxys 87/375 Yield

Conditions & References

82 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

O N O

F N

Rx-ID: 38266876 View in Reaxys 88/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice

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Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O N

(+)-enantiomer,rel-configuration

F (-)-enantiomer,rel-configuration

Rx-ID: 38266877 View in Reaxys 89/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 90 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

N O

Cl N

Rx-ID: 2104264 View in Reaxys 90/375 Yield 98 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

96 %

95 %

94 %

88 %

With nickel(II) ferrite, isopropyl alcohol, Time= 3h, T= 80 °C , Green chemistry Payra, Soumen; Saha, Arijit; Banerjee, Subhash; RSC Advances; vol. 6; nb. 57; (2016); p. 52495 - 52499 View in Reaxys

82 %

With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, Time= 1h, Heating

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Chikashita, Hidenori; Morita, Yasuhiro; Itoh, Kazuyoshi; Synthetic Communications; vol. 15; nb. 6; (1985); p. 527 - 534 View in Reaxys 82 %

50 % Turn- With tri-n-butyl-tin hydride in dichloromethane, Time= 2h, Ambient temperature, var. temperatures, var. solvents, ov. Product distribution Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1) methylene chloride, room temp., 20h, 2) methanol, -15 deg C, Yield given. Multistep reaction Palomo, Claudio; Aizpurua, Jesus M.; Cossio, Fernando P.; Garcia, Jesus M.; Lopez, M. Concepcion; Oiarbide, Mikel; Journal of Organic Chemistry; vol. 55; nb. 7; (1990); p. 2070 - 2078 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1.) methylene chloride, 20-24h, room temperature; 2.) MeOH, methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, T= 20 °C , Inert atmosphere, Reflux Zhang, Fanglin; Wei, Mohui; Dong, Junfang; Zhou, Yirong; Lu, Dengfu; Gong, Yuefa; Yang, Xiangliang; Advanced Synthesis and Catalysis; vol. 352; nb. 17; (2010); p. 2875 - 2880 View in Reaxys > 95 %Spectr.

O N

Cl N

Rx-ID: 2104276 View in Reaxys 91/375 Yield 67 %

Conditions & References in water, Time= 73h, T= 31 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

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Rx-ID: 3230159 View in Reaxys 92/375 Yield

Conditions & References

73 %

in water, Time= 72h, T= 31 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Z N

Cl N

Rx-ID: 3961179 View in Reaxys 93/375 Yield

Conditions & References

82 %

O O

O E

Rx-ID: 24435058 View in Reaxys 94/375 Yield 48%

Conditions & References 46.3 : Step 3 Step 3 2-(3-Chlorophenyl)-1-nitroethane A solution of 13.5 g (72 mmol) of 2-(3-Chlorophenyl)-1-nitroethene, from Step 2, in 200 mL of dioxane was added dropwise to a stirred suspension of 6 g (157 mmol) of sodium borohydride in a mixture of 140 mL of dioxane and 60 mL of ethanol. The reaction mixture was stirred at ambient temperature for 2 h and then the excess borohydride was quenched with acid. The reaction mixture was concentrated in vacuo and the residue was partitioned between methylene chloride and water (4:1). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified on silica gel eluted with 20percent methylene chloride in hexane to afford 6.3 g (48percent yield) of the title compound; MS DCI-NH3 M/Z: 203 (M+NH4)+; 1 H NMR (CDCl3) δ3.3 (2H, t, J=7.5 Hz), 4.6 (2H, t, J=7.5 Hz), 7.05-7.3 (4H, m). With sodium borohydride in 1,4-dioxane, ethanol, hexane Patent; Abbott Laboratories; US5180733; (1993); (A1) English View in Reaxys

48%

46.3 : Step 3: Step 3: 2-(3-Chlorophenyl)-1-nitroethane A solution of 13.5 g (72 mmol) of 2-(3-Chlorophenyl)-1-nitroethene, from Step 2, in 200 mL of dioxane was added dropwise to a stirred suspension of 6 g (157 mmol) of sodium borohydride in a mixture of 140 mL of dioxane and 60 mL of ethanol. The reaction mixture was stirred at ambient temperature for 2 h and then the excess borohydride was quenched with acid. The reaction mixture was concentrated in vacuo and the residue was partitioned between methylene chloride and water (4:1). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure.

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The residue was purified on silica gel eluted with 20percent methylene chloride in hexane to afford 6.3 g (48percent yield) of the title compound; MS DCl--NH3 M/Z: 203 (M+NH4)+; 1 H NMR (CDCl3) δ3.3 (2H, t, J=7.5 Hz), 4.6 (2H, t, J= 7.5 Hz), 7.05-7.3 (4H, m). With sodium borohydride in 1,4-dioxane, ethanol, hexane Patent; Abbott Laboratories; US5248677; (1993); (A1) English View in Reaxys O

Rx-ID: 29961057 View in Reaxys 95/375 Yield 94 %

Conditions & References With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 1h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

94 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, T= 20 °C , Inert atmosphere, Reflux Zhang, Fanglin; Wei, Mohui; Dong, Junfang; Zhou, Yirong; Lu, Dengfu; Gong, Yuefa; Yang, Xiangliang; Advanced Synthesis and Catalysis; vol. 352; nb. 17; (2010); p. 2875 - 2880 View in Reaxys

398 mg

F N

O F

Rx-ID: 23674459 View in Reaxys 96/375 Yield 62 %

Conditions & References 22 :Add portionwise sodium borohydride (12 g) over 1.5 h to a solution of 1,3- difluoro-5- (2-nitrovinyl)-benzene (100 g) in a mixture of dimethylsulfoxide (400 mL) and acetic acid (80 mL) at room temperature using a water bath to keep the temperature below 30 °C. Dilute with ethyl acetate (1000 mL) and wash with water (600 mL), saturated aqueous sodium bicarbonate (2 x 600 mL), saturated aqueous sodium chloride (600 mL), dry (magnesium sulfate) concentrate and purify (silica gel chromatography, eluting with 3: 97 ethyl acetate: hexanes) to give the title compound a pale yellow solid (63 g, 62percent).

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With sodium tetrahydroborate in acetic acid, dimethyl sulfoxide, Time= 1.5h, T= 20 - 30 °C Patent; ELI LILLY AND COMPANY; WO2005/108358; (2005); (A2) English View in Reaxys 62%

1 :3,5-Difluorophenyl nitroethane Add portionwise sodium borohydride (12 g) over 1.5 hours to a solution of 1,3-difluoro-5-(2-nitrovinyl)-benzene (100 g) in a mixture of dimethylsulfoxide (400 mL) and acetic acid (80 mL) at room temperature using a water bath to keep the temperature below 30° C. Dilute with ethyl acetate (1000 mL) and wash with water (600 mL), saturated aqueous sodium bicarbonate (2*600 mL), saturated aqueous sodium chloride (600 mL), dry (magnesium sulfate) concentrate and purify (silica gel chromatography, eluding with 3:97 ethyl acetate:hexanes) to give the title compound as a pale yellow liquid (63 g, 62percent). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, T= 30 °C Patent; Broughton, Howard Barff; Dally, Robert Dean; Durham, Timothy Barrett; Gonzalez-Garcia, Maria Rosario; Sa, Lilly; Hahn, Patric James; Henry, Kenneth James; Kohn, Todd Jonathan; McCarthy, James Ray; Shepherd, Timothy Alan; Erickson, Jon Andre; Bueno Melendo, Ana Belen; US2007/225267; (2007); (A1) English View in Reaxys F

F N

E N

Rx-ID: 28376780 View in Reaxys 97/375 Yield 95 %

Conditions & References 34.C :Step C: 3,5-difluoro-5-(2-nitro-ethyl)benzene 3,5-difluoro-5-[(E)-2-nitrovinyl]benzene (1.1 g, 6.02 mmol) obtained in Step B was placed in DMSO and acetic acid solution, and NaBH4 (91 mg, 24.08 mmol) was added thereto. The reaction solution was stirred below 30 °C for 1.5 hours. After the reaction was complete, the reaction solution was diluted with EtOAc, washed with H2O and NaHCO3, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by column chromatography (2- propanol/chloroform = 1/4) to afford the title compound (1.08 g, 95percent). With acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 30 °C Patent; LG LIFE SCIENCES, LTD.; WO2009/38411; (2009); (A2) English View in Reaxys

N O

N N

Rx-ID: 2071830 View in Reaxys 98/375 Yield 99 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

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With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1.) methylene chloride, 20-24h, room temperature; 2.) MeOH, methylene chloride, Multistep reaction Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys

N N

Rx-ID: 2766384 View in Reaxys 99/375 Yield

Conditions & References

52 %

48 %

in water, Time= 65h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

O O

N E

Rx-ID: 3646464 View in Reaxys 100/375 Yield

Conditions & References

52 %

in water, Time= 67h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys O N

O N

Rx-ID: 33657770 View in Reaxys 101/375 Yield 82 %

Conditions & References 4.2. Typical procedure for the reduction of conjugated nitroalkenes General procedure: The mixture of nitroalkenes 1 (0.1 g, 0.67 mmol), Hantzsch ester (0.19 g, 0.74 mmol) and Sbenzyl isothiouronium chloride (14 mg, 0.067 mmol) in methanol (5 ml) was stirred at 60 °C for 5-12 h. After completion of the reaction, the crude product in methanol was concentrated and added into the excess cooled CH2Cl2. The S-benzyl isothiouronium chloride was readily precipitated out, and then filtered and washed many times with CH2Cl2 to be reused. The filtrate was evaporated and the residue was purified by flash column chromatography to give the required nitroalkanes products 2. All nitroalkanes except 2j and 2p were characterized with the reported spectroscopic data. [2] and [5] With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, S-benzyl isothiouronium chloride in methanol, T= 60 °C , Inert atmosphere Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron; vol. 68; nb. 32; (2012); p. 6513 6516 View in Reaxys

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O N

Rx-ID: 292799 View in Reaxys 102/375 Yield

Conditions & References With methanol, palladium on activated charcoal, T= 29 - 36 °C , p= 11032.6 - 25742.8Torr , Hydrogenation Patent; Comm. Solv. Corp.; US2483201; (1945) View in Reaxys

Z N

N O

Rx-ID: 4019208 View in Reaxys 103/375 Yield

Conditions & References

84 %

With PBI in butan-1-ol, Time= 9h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

O O

Rx-ID: 8839823 View in Reaxys 104/375 Yield

Conditions & References

23 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

Rx-ID: 8839990 View in Reaxys 105/375 Yield

Conditions & References

16 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

O N

O N O

Rx-ID: 8840095 View in Reaxys 106/375 Yield 52 %

Conditions & References With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

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N O

Rx-ID: 2106801 View in Reaxys 107/375 Yield

Conditions & References

88 %

With zinc(II) tetrahydroborate in DME, Time= 12h, T= 0 - 5 °C Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

88 %

With zinc(II) tetrahydroborate in DME, Time= 12h, T= 0 °C Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

N O

Rx-ID: 2106809 View in Reaxys 108/375 Yield

Conditions & References

80 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys O

NH N

NH 2

Rx-ID: 18162347 View in Reaxys 109/375 Yield

Conditions & References Reaction Steps: 2 1: NaBH4 / ethanol / 5 h 2: conc. HCl / ethanol / 2 h / Heating With hydrogenchloride, sodium tetrahydroborate in ethanol Florvall; Persson; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 36; nb. 3 B; (1982); p. 141 - 146 View in Reaxys

H 2N

O N

H 2N

Rx-ID: 3390611 View in Reaxys 110/375 Yield 72 % Chromat., 85 % 85 %, 72 % Chromat.

Conditions & References in ethanol, Heating Itoh, Kazuyoshi; Ishida, Hideaki; Chikashita, Hidenori; Chemistry Letters; (1982); p. 1117 - 1118 View in Reaxys in ethanol, Heating Itoh, Kazuyoshi; Ishida, Hideaki; Chikashita, Hidenori; Chemistry Letters; (1982); p. 1117 - 1118

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View in Reaxys

O N

Rx-ID: 1062959 View in Reaxys 111/375 Yield

Conditions & References

88 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 5h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

55 %

With sodium tetrahydroborate in tetrahydrofuran, methanol, Time= 0.666667h, T= 20 °C Merlino, Alicia; Boiani, Mariana; Cerecetto, Hugo; Gonzalez, Mercedes; Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy; vol. 67; nb. 2; (2007); p. 540 - 549 View in Reaxys With sodium tetrahydroborate Bailey,K. et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 3143 - 3151 View in Reaxys

O O

Rx-ID: 1063084 View in Reaxys 112/375 Yield

Conditions & References

85 %

O O

Rx-ID: 1063587 View in Reaxys 113/375 Yield 72 %

Conditions & References With sodium tetrahydroborate, sodium hydroxide in ethanol, Time= 1h, T= 0 °C

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Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys With sodium tetrahydroborate Bailey,K. et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 3143 - 3151 View in Reaxys

O N

Rx-ID: 2106106 View in Reaxys 114/375 Yield

Conditions & References

100 %

66 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

43 %

42 %

in water, Time= 75h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O O

O E

Rx-ID: 2194637 View in Reaxys 115/375 Yield 68 %

60 %

in water, Time= 50h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881

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View in Reaxys

O N

Rx-ID: 8813858 View in Reaxys 116/375 Yield

Conditions & References

72 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

Rx-ID: 36298026 View in Reaxys 117/375 Yield

O N

Rx-ID: 36298028 View in Reaxys 118/375 Yield

O O

O E

O O

Rx-ID: 38266869 View in Reaxys 119/375 Yield

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O N

Rx-ID: 38266874 View in Reaxys 120/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 62 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O N

Rx-ID: 45635806 View in Reaxys 121/375 Yield

Conditions & References Reaction Steps: 2 1: silica gel; sodium tetrahydroborate / isopropyl alcohol; chloroform 2: (2,9-dimethyl-4,7-diphenyl-1,10-phenantroline)NiBr2; diethylzinc / tert-butyl methyl ether; 1,4-dioxane / 24 h / 40 °C / Inert atmosphere; Sealed tube; Glovebox With sodium tetrahydroborate, (2,9-dimethyl-4,7-diphenyl-1,10-phenantroline)NiBr2, diethylzinc, silica gel in 1,4-dioxane, tert-butyl methyl ether, chloroform, isopropyl alcohol Rezazadeh, Sina; Devannah, Vijayarajan; Watson, Donald A.; Journal of the American Chemical Society; vol. 139; nb. 24; (2017); p. 8110 - 8113 View in Reaxys

Rx-ID: 2074202 View in Reaxys 122/375 Yield 97 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

83 %

With hantzsch ester in water, Time= 24h, T= 100 °C , Green chemistry, chemoselective reaction He, Qi; Xu, Zhihong; Jiang, Dehong; Ai, Wensi; Shi, Ronghua; Qian, Shan; Wang, Zhouyu; RSC Advances; vol. 4; nb. 17; (2014); p. 8671 - 8674 View in Reaxys With hydrogen fluoride dimer, tri-n-butyl-tin hydride, 1.) methylene chloride, 20-24h, room temperature; 2.) MeOH, methylene chloride, Multistep reaction

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Aizpurua, J. M.; Oiarbide, M.; Palomo, C.; Tetrahedron Letters; vol. 28; nb. 44; (1987); p. 5365 - 5366 View in Reaxys With benzaldehyde, 1,2-diaminobenzene in butan-1-ol, T= 20 °C , Inert atmosphere, Reflux Zhang, Fanglin; Wei, Mohui; Dong, Junfang; Zhou, Yirong; Lu, Dengfu; Gong, Yuefa; Yang, Xiangliang; Advanced Synthesis and Catalysis; vol. 352; nb. 17; (2010); p. 2875 - 2880 View in Reaxys O

O N

N O

O N O

Rx-ID: 2074208 View in Reaxys 123/375 Yield 99 %

97 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 1h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

91 %

90 %

87 %

With nickel(II) ferrite, isopropyl alcohol, Time= 3h, T= 80 °C , Green chemistry Payra, Soumen; Saha, Arijit; Banerjee, Subhash; RSC Advances; vol. 6; nb. 57; (2016); p. 52495 - 52499 View in Reaxys

61 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

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With benzaldehyde, 1,2-diamino-benzene in butan-1-ol, T= 20 °C , Inert atmosphere, Reflux Zhang, Fanglin; Wei, Mohui; Dong, Junfang; Zhou, Yirong; Lu, Dengfu; Gong, Yuefa; Yang, Xiangliang; Advanced Synthesis and Catalysis; vol. 352; nb. 17; (2010); p. 2875 - 2880 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhao, Xinyang; Wang, Xinbo; Liu, Qisong; Li, Zigang; Wang, David Zhigang; Angewandte Chemie - International Edition; vol. 51; nb. 32; (2012); p. 8050 - 8053 View in Reaxys O

O N

NH 2 N

Rx-ID: 2107683 View in Reaxys 124/375 Yield

Conditions & References

5 %, 44 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

44 %, 5 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

O O

Rx-ID: 2134142 View in Reaxys 125/375 Yield

Conditions & References

75 %

With sodium cyanoborohydride, zeolite H-ZSM5 in methanol, Time= 1h, pH 6.5 Gupta, Anuradha; Haque, Azizul; Vankar, Yashwant D.; Chemical Communications; nb. 14; (1996); p. 1653 1654 View in Reaxys

42 %

in water, Time= 70h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys O

O O

Rx-ID: 2153346 View in Reaxys 126/375 Yield 76 %

Conditions & References With tris(pentafluorophenyl)-borane in dichloromethane, Time= 10h, T= 20 °C Chandrasekhar, Srivari; Chandrashekar, Gudise; Reddy, Marepally Srinivasa; Srihari, Pabbaraja; Organic and Biomolecular Chemistry; vol. 4; nb. 9; (2006); p. 1650 - 1652 View in Reaxys

65 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

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O O

N O

Rx-ID: 3962550 View in Reaxys 127/375 Yield

Conditions & References

91 %

O O

Rx-ID: 4040655 View in Reaxys 128/375 Yield 96 %

Conditions & References With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 0.5h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

95 %

With sodium tetrahydroborate in methanol, Time= 1.5h, T= 20 °C , Inert atmosphere Anderson, James C.; Noble, Adam; Torres, Pascual Ribelles; Tetrahedron Letters; vol. 53; nb. 42; (2012); p. 5707 - 5710 View in Reaxys

93 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

92 %

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75 %

With sodium tetrahydroborate in methanol, Time= 0.75h, T= 20 °C Yu; Liu; Hu; Journal of Organic Chemistry; vol. 66; nb. 3; (2001); p. 919 - 924 View in Reaxys

75 %

With hantzsch ester in water, Time= 24h, T= 100 °C , Green chemistry, chemoselective reaction He, Qi; Xu, Zhihong; Jiang, Dehong; Ai, Wensi; Shi, Ronghua; Qian, Shan; Wang, Zhouyu; RSC Advances; vol. 4; nb. 17; (2014); p. 8671 - 8674 View in Reaxys With sodium tetrahydroborate Baxter,I.; Swan,G.A.; Journal of the Chemical Society [Section] C: Organic; (1968); p. 468 - 470 View in Reaxys With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate in neat (no solvent), T= 100 °C Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831 View in Reaxys

O N

Rx-ID: 4770027 View in Reaxys 129/375 Yield

Conditions & References

With yeast, water in Petroleum ether, Time= 24h, Ambient temperature Bak, Radoslaw R.; McAnda, Anita F.; Smallridge, Andrew J.; Trewhella, Maurie A.; Australian Journal of Chemistry; vol. 49; nb. 11; (1996); p. 1257 - 1260 View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol Burkhard, Johannes A.; Tchitchanov, Boris H.; Carreira, Erick M.; Angewandte Chemie - International Edition; vol. 50; nb. 23; (2011); p. 5379 - 5382 View in Reaxys

O O

Rx-ID: 30636176 View in Reaxys 130/375 Yield

Conditions & References Reaction Steps: 2 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: pyridine; methanol-d4 / 35 h / Reflux; Inert atmosphere With pyridine, sodium tetrahydroborate, methanol-d4, sodium hydroxide in ethanol Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

N O

O OH

N O

O OH

Rx-ID: 2194879 View in Reaxys 131/375

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Yield

Conditions & References

85 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys

73 %

With sodium tetrahydroborate in tetrahydrofuran, methanol Tius; Kerr; Journal of the American Chemical Society; vol. 114; nb. 15; (1992); p. 5959 - 5966 View in Reaxys

O N

O HO

Rx-ID: 2550401 View in Reaxys 132/375 Yield

Conditions & References

81 %

With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, T= 20 °C Zhang, Bang-Le; Wang, Fang-Dao; Yue, Jian-Min; Synlett; nb. 4; (2006); p. 567 - 570 View in Reaxys

80 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys HO

HO O

E N

Rx-ID: 2550515 View in Reaxys 133/375 Yield

Conditions & References

78 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys

HO E

Rx-ID: 9523679 View in Reaxys 134/375 Yield 96 %

Conditions & References With sodium tetrahydroborate in tetrahydrofuran, methanol, T= 0 - 20 °C Wang, Jianjun; Evano, Gwilherm; Organic Letters; vol. 18; nb. 15; (2016); p. 3542 - 3545 View in Reaxys

71 %

With (3,5-(CF3)2C6H3NH)2C=S, 2,6-di(Me)-1,4-dihydropyridine-3,5-di(COOEt) in dichloromethane, Time= 24h, Heating Zhang, Zhiguo; Schreiner, Peter R.; Synthesis; nb. 16; (2007); p. 2559 - 2564 View in Reaxys With sodium tetrahydroborate Cederbaum, Fredrik; De Mesmaeker, Alain; Jeanguenat, Andre; Kempf, Hans-Joachim; Lamberth, Clemens; Schnyder, Anita; Zeller, Martin; Zeun, Ronald; Chimia; vol. 57; nb. 11; (2003); p. 680 - 684 View in Reaxys

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O N

Rx-ID: 15254786 View in Reaxys 135/375 Yield

Conditions & References Reaction Steps: 2 1: 70 percent / NaBH4 / methanol / 1 h / 20 °C 2: 73 percent / BBr3 / CH2Cl2 / 0.75 h / 0 - 20 °C With sodium tetrahydroborate, boron tribromide in methanol, dichloromethane El Hadri; Nicolle; Guillaume; Leclerc; Pietri-Rouxel; Strosberg; Archimbault; Pharmazie; vol. 56; nb. 7; (2001); p. 517 - 522 View in Reaxys

O O

Rx-ID: 29831105 View in Reaxys 136/375 Yield

Conditions & References

89 %

HO HO

O N

Rx-ID: 33683087 View in Reaxys 137/375 Yield 68 %

Conditions & References 4.1.2. General procedure 2 for the synthesis of 2-aryl-1-nitroethanes 4 and 5 General procedure: To a flask containing the corresponding 2-aryl-1-nitroethene were added silica gel (2 g per mmol of starting material), and 1.5 mL of 2-propanol and 8 mL of chloroform per gram of silica gel [53]. To this mixture were added 4 mmol of NaBH4 per mmol of starting material in small amounts and the resulting mixture was allowed to stir at room temperature until the complete disappearance of the 2-aryl-1-nitroethene (usually noted after a reaction time of about 30 min). The reaction mixture was quenched with an aqueous solution of 0.1 N HCl, filtered to eliminate the silica gel and evaporated under vacuum to eliminate 2-propanol and chloroform. The resulting aqueous mixture was then extracted by CH2Cl2 (3.x.). The organic phase was dried over MgSO4, filtered and concentrated under vacuum. Crude product was purified by chromatography on silica gel in order to afford the desired compound. With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.5h, T= 20 °C Mur Blanch, Nuria; Chabot, Guy G.; Quentin, Lionel; Scherman, Daniel; Bourg, Stephane; Dauzonne, Daniel; European Journal of Medicinal Chemistry; vol. 54; (2012); p. 22 - 32 View in Reaxys

Rx-ID: 43305734 View in Reaxys 138/375 Yield 32.0 g

Conditions & References 1.1 :Obtained in the previous step B (33.6g, 172.3mmol) was added 1,4-dioxane (500mL), stirred vigorously, making it a turbid liquid. To an eggplant-shaped flask was succesively added ethanol (75mL), 1,4-dioxane (300mL), NaBH4 (32.0g, 845.9mmol), added dropwise with stirring, the addition was complete within about 1h. Stirred at room temper-

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ature overnight. Solution gradually turns orange. The next day the system was added ice water 250ml, the system adjusted with a weak acid glacial acetic acid, transferred into a separatory funnel and extracted with ethyl acetate, the organic layer was washed with water, saturated brine, ethyl acetate was removed under reduced pressure to give a red-brown oil C (32.0g, 162.4mmol). With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C Patent; Chengdu Bestchiralbio Limited-Liability Company; Li, Dequn; (64 pag.); CN105481849; (2016); (A) Chinese View in Reaxys O

S N

Rx-ID: 29531586 View in Reaxys 139/375 Yield

Conditions & References

89 %

With sodium tetrahydroborate, silica gel, isopropyl alcohol in dichloromethane, T= 20 °C Cloonan, Suzanne M.; Keating, John J.; Corrigan, Desmond; O'Brien, John E.; Kavanagh, Pierce V.; Williams, D. Clive; Meegan, Mary J.; Bioorganic and Medicinal Chemistry; vol. 18; nb. 11; (2010); p. 4009 - 4031 View in Reaxys 4.1.3. General procedure A: preparation of 1-aryl-1-nitroethanes General procedure: Sodium borohydride (15.00 mmol, 5.70 g) was added to a vigorously stirred mixture of the appropriate nitroethene (3.68 mmol), silica gel (9.30 g) and propan-2-ol (100 mL) in dichloromethane (350 mL) at room temperature. The mixture was stirred at room temperature for 20 min until the solution turned colourless. Excess NaBH4 was quenched with the addition of dilute HCl (50 mL). The mixture was filtered and the silica gel washed with dichloromethane (100 mL). All organic phases were combined and washed with brine (3 .x. 50 mL) and water (3 .x. 50 mL). The organic phases were then dried over anhydrous Mg2SO4 and the solvent removed in vacuo. The crude product was purified by column chromatography over silica gel. With sodium tetrahydroborate, silica gel in dichloromethane, isopropyl alcohol, Time= 0.333333h, T= 20 °C McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Guenther H.; Meegan, Mary J.; Williams, D. Clive; Bioorganic and Medicinal Chemistry; vol. 19; nb. 3; (2011); p. 1328 - 1348 View in Reaxys

O N

Cl N

Rx-ID: 2138704 View in Reaxys 140/375 Yield 73 %

Conditions & References in water, Time= 64h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

51 %

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O O

Rx-ID: 2153093 View in Reaxys 141/375 Yield 52 %

48 %

O O

O Cl

Rx-ID: 2153095 View in Reaxys 142/375 Yield 65 %

Conditions & References 4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

47 %

With baker's yeast in ethanol, water, Time= 24h, T= 35 °C Kawai, Yasushi; Inaba, Yoshikazu; Tokitoh, Norihiro; Tetrahedron Asymmetry; vol. 12; nb. 2; (2001); p. 309 - 318 View in Reaxys

42 %

in water, Time= 50h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys With D-glucose, glucose dehydrogenase CDX901, ene reductase DBVPG from Lycopersicon escultentum, NADPH in aq. phosphate buffer, Time= 24h, T= 20 °C , pH= 7, Enzymatic reaction, Reagent/catalyst Reß, Tina; Hummel, Werner; Hanlon, Steven P.; Iding, Hans; Gröger, Harald; ChemCatChem; vol. 7; nb. 8; (2015); p. 1302 - 1311 View in Reaxys

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Cl N

Rx-ID: 11098387 View in Reaxys 143/375 Yield

Conditions & References

64 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 3h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

52 %

O Cl

Z N

O N

Rx-ID: 28714429 View in Reaxys 144/375 Yield

Conditions & References With Glc 6P, pentaerythritol tetranitrate reductase, NADP+, glucose 6-phosphate dehydrogenase in 2,2,4-trimethylpentane, ortho-methylpropylbenzene, Time= 168h, T= 30 °C , pH= 7, aq. phosphate buffer, Inert atmosphere, Enzymatic reaction, optical yield given as percent ee, enantioselective reaction Toogood, Helen S.; Fryszkowska, Anna; Hare, Victoria; Fisher, Karl; Roujeinikova, Anna; Leys, David; Gardiner, John M.; Stephens, Gill M.; Scrutton, Nigel S.; Advanced Synthesis and Catalysis; vol. 350; nb. 17; (2008); p. 2789 - 2803 View in Reaxys

O N O

O N

Rx-ID: 28714432 View in Reaxys 145/375 Yield

65/143

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With glucose-6-phosphate dehydrogenase, glucose-6-phosphate, pentaerythritol tetranitrate reductase T26S mutant, NADPH in 2,2,4-trimethylpentane, ortho-methylpropylbenzene, Time= 168h, T= 30 °C , pH= 7, aq. phosphate buffer, Enzymatic reaction Hulley, Martyn E.; Toogood, Helen S.; Fryszkowska, Anna; Mansell, David; Stephens, Gill M.; Gardiner, John M.; Scrutton, Nigel S.; ChemBioChem; vol. 11; nb. 17; (2010); p. 2433 - 2447 View in Reaxys With glucose-6-phosphate dehydrogenase, G-6-P, wild type pentaerythritol tetranitrate reductase, NADPH in N,Ndimethyl-formamide, Time= 48h, T= 30 °C , phosphate buffer, Inert atmosphere, anaerobic, Enzymatic reaction, enantioselective reaction Toogood, Helen S.; Fryszkowska, Anna; Hulley, Martyn; Sakuma, Michiyo; Mansell, David; Stephens, Gill M.; Gardiner, John M.; Scrutton, Nigel S.; ChemBioChem; vol. 12; nb. 5; (2011); p. 738 - 749 View in Reaxys O

Rx-ID: 33493015 View in Reaxys 146/375 Yield

Conditions & References

98 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 2h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

Rx-ID: 36298023 View in Reaxys 147/375 Yield

Conditions & References With glucose dehydrogenase, D-Glucose, NADPH, citric acid in aq. phosphate buffer, ethanol, Time= 10h, T= 9 °C , pH= 6, Sonication, Reagent/catalyst, enantioselective reaction Burda, Edyta; Reß, Tina; Winkler, Till; Giese, Carolin; Kostrov, Xenia; Huber, Tobias; Hummel, Werner; Gröger, Harald; Angewandte Chemie - International Edition; vol. 52; nb. 35; (2013); p. 9323 - 9326; Angew. Chem.; vol. 125; nb. 35; (2013); p. 9493 - 9496 View in Reaxys

O N O

Cl (+)-enantiomer,rel-configuration

Cl (-)-enantiomer,rel-configuration

Rx-ID: 38266801 View in Reaxys 148/375

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Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 95 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O N

(-)-enantiomer,rel-configuration

(+)-enantiomer,rel-configuration

Rx-ID: 38266806 View in Reaxys 149/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 50 °C , p= 45603.1Torr , Autoclave, Overall yield = 45 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys O

N O

Rx-ID: 38266863 View in Reaxys 150/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O O

N O

Rx-ID: 38266864 View in Reaxys 151/375 Yield

O NH 2

N O

Rx-ID: 40573293 View in Reaxys 152/375 Yield

Conditions & References Reaction Steps: 2 1: diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate / neat (no solvent) / 100 °C 2: hydrogen; palladium on activated charcoal / methanol With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, palladium on activated charcoal, hydrogen in methanol Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831

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View in Reaxys O

O O

O N

NH 2

Rx-ID: 40573296 View in Reaxys 153/375 Yield

Conditions & References Reaction Steps: 2 1: diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate / neat (no solvent) / 100 °C 2: hydrogen; palladium on activated charcoal / methanol With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, palladium on activated charcoal, hydrogen in methanol Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831 View in Reaxys

Rx-ID: 2042362 View in Reaxys 154/375 Yield 93 %

Conditions & References With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, Time= 2h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

86 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 4h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

79 %

N O

Rx-ID: 2089618 View in Reaxys 155/375

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Yield

Conditions & References

98 %

94 %

With hantzsch ester in water, Time= 24h, T= 100 °C , Green chemistry, chemoselective reaction He, Qi; Xu, Zhihong; Jiang, Dehong; Ai, Wensi; Shi, Ronghua; Qian, Shan; Wang, Zhouyu; RSC Advances; vol. 4; nb. 17; (2014); p. 8671 - 8674 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhao, Xinyang; Wang, Xinbo; Liu, Qisong; Li, Zigang; Wang, David Zhigang; Angewandte Chemie - International Edition; vol. 51; nb. 32; (2012); p. 8050 - 8053 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

2.7 g

With sodium tetrahydroborate in acetic acid, dimethyl sulfoxide, Time= 0.5h, Inert atmosphere, Schlenk technique Reddy, Golipalli Ramana; Mukherjee, Debopreeti; Chittoory, Arjun Kumar; Rajaram, Sridhar; Organic Letters; vol. 16; nb. 22; (2014); p. 5874 - 5877 View in Reaxys 3.B : 2-(2-Nitroethyl)naphthalene Step B 2-(2-Nitroethyl)naphthalene To a suspension of sodium borohydride (4 g) in a mixture of dioxane (85 ml) and ethanol (30 ml) was added dropwise a solution of 2-(2-nitroethenyl)naphthalene (100 g) in dioxane (90 ml) over 30 minutes. The flask was cooled with a cold water bath during addition. Stirring was maintained for an additional 11/2hours. Ice (100 ml) and 50percent aqueous acetic acid room temperature, concentrated in vacuo and extracted with methylene chloride. The organic layer was washed with water, saturated aqueous sodium chloride and dried over magnesium sulfate. The solvent was evaporated in vacuo to yield an oil which was crystallized from acetic acid to give the title compound (6.79 g) as a yellow solid, m.p. 59°-60° C. With sodium borohydrid, acetic acid in 1,4-dioxane, ethanol Patent; Merrell Dow Pharmaceuticals Inc.; US5041673; (1991); (A1) English View in Reaxys

N Z

N O

Rx-ID: 3961395 View in Reaxys 156/375 Yield 80 %

Conditions & References With PBI in butan-1-ol, Time= 1h, Heating Chikashita, Hidenori; Nishida, Shuichi; Miyazaki, Makoto; Morita, Yasuhiro; Itoh, Kazuyoshi; Bulletin of the Chemical Society of Japan; vol. 60; nb. 2; (1987); p. 737 - 746 View in Reaxys

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E N

Rx-ID: 9313014 View in Reaxys 157/375 Yield

Conditions & References

57 %

1.2 : Step 2) Synthesis of 1- (2-nitroethyl) naphthalene (E) -1- (2-nitroethenyl) naphthalene (0.598 g, 3.0 mmol) and anhydrous methanol (20 mL) were added successively to 100 ml single mouth bottle,0 & lt; 0 & gt; C was slowly added portionwise sodium borohydride (0.290 g, 7.5 mmol)After 2 hours,The reaction is complete,Stop the reaction.To the reaction solution was slowly added an ice-water mixture (30 mL)Extracted with dichloromethane (30 mL x 3)Combine organic phase,And washed with saturated brine (30 mL)The organic layer was dried over anhydrous sodium sulfate.filter,The filtrate was evaporated under reduced pressure and purified by column chromatography(Petroleum ether / ethyl acetate (v / v) = 100/1)To give the title compound (yellow liquid, 0.344 g,57percent). With methanol, sodium tetrahydroborate, Time= 2h, T= 0 °C Patent; Guangdong HEC Pharmaceutical Co., Ltd.; Jin, Chuanfei; Gao, Jinheng; Zhang, Yingjun; (39 pag.); CN106243052; (2016); (A) Chinese View in Reaxys With hydrogen, polymeric rhodium in tetrahydrofuran, ethanol, Time= 72h, p= 2585.74Torr Arstad, Erik; Barrett, Anthony G. M.; Tedeschi, Livio; Tetrahedron Letters; vol. 44; nb. 13; (2003); p. 2703 - 2707 View in Reaxys 5.B : 1-(2-Nitroethyl)naphthalene Step B 1-(2-Nitroethyl)naphthalene 1-(2-Nitroethenyl)naphthalene (16.1 g) was reduced to the title compound according to the procedure described in Example 3 Step B. The crude product was crystallized from a methylene chloride/cyclohexane mixture to give the title compound (6.27 g) as a yellow solid. The crystallization residue was chromatographed (silica gel, elution with cyclohexane:ethyl acetate, 95:5) and the purified product was recrystallized from pentane/diethyl ether to yield the title compound (6.1 g) as white needles, m.p. 45°-46° C. Patent; Merrell Dow Pharmaceuticals Inc.; US5041673; (1991); (A1) English View in Reaxys

Cl O

N F

N O

Rx-ID: 25915470 View in Reaxys 158/375 Yield 70%

Conditions & References 188 :1-Chloro-3-fluoro-5-(2-nitroethyl)-benzene Add sodium borohydride (0.75 g, 19.7 mmol) to a solution of 1,4-dioxane (10 mL) and absolute ethanol (2.5 mL) in a room temperature water bath. Next add 1-chloro-3-fluoro-5-((E)-2-nitrovinyl)-benzene (1.5 g, 8.98 mmol) in 1,4-dioxane (10 mL) dropwise and stir at room temperature for 1 hour (Bhattacharjya, Synthesis, 1985, 886-997). Add ice chips, glacial acetic acid (2 mL), water (2 mL), concentrate and dilute in dichloromethane/water. Wash the dichloromethane layer with water, saturated aqueous sodium chloride, dry (sodium sulfate), filter and purify (silica gel chromatography, eluding with 1:1 dichloromethane:hexanes) to give the desired compound as an oil (1.07 g 70percent). 1H NMR (CDCl ) δ 3.30 (t, 2H, J=8 Hz), 4.62 (t, 2H, J=8 Hz), 6.85 (m, 1H), 7.02 (m, 2H) 3 Stage 1: With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1h, T= 20 °C Stage 2: With acetic acid in 1,4-dioxane, ethanol, water, T= 0 °C

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Patent; Broughton, Howard Barff; Dally, Robert Dean; Durham, Timothy Barrett; Gonzalez-Garcia, Maria Rosario; Sa, Lilly; Hahn, Patric James; Henry, Kenneth James; Kohn, Todd Jonathan; McCarthy, James Ray; Shepherd, Timothy Alan; Erickson, Jon Andre; Bueno Melendo, Ana Belen; US2007/225267; (2007); (A1) English View in Reaxys F

O F

F O N

F F

Rx-ID: 41905555 View in Reaxys 159/375 Yield 90 %

Conditions & References 2 : Example 2Synthesis of 3-(2,4,5-trifluorophenyl)-nitroethane (4) Example 2Synthesis of 3-(2,4,5-trifluorophenyl)-nitroethane (4):3-nitrostyrene (3) (5 g, 24.63 mmol) was dissolved in iPrOH (1 g) and CHC13 (20 mL) with silica gel (1 g) and to this system sodium borohydride (1.86 g, 49.26 mmol, 2 equv) was added over ‘/2 h at 27 °C. Dilute HCL (25 mL) was added to decompose the excess NaBH4 Thereaction mixture was stirred at 27 °C, and the advancement of the reaction was observed by TLC (1:9, Ethyl acetate/ Hexane). When the reaction was completed, the reaction mixture was filtered. The filtrate is extracted with DCM and washed with 1percent HC1 acid (25 mL). The organic phase was dried with anhydrous Na2SO4, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography. The column was packed in hexane and run in10percent ethyl acetate in hexane solvent system to afford 4 (4.54 g, 22.16 mmol, 90percent) as Yellowish gum. The spectral analysis of the compound is Compound 4:Rf = 0.42 (Hexane/EtOAc 9:1); 1H NMR (300 MHz, CDC13) ö 4.64 (t, J = 13.83 Hz, 2H, CH2CH2NO2), 3.32 (t, J = 13.8 Hz, 2H, CH2CH2NO2), 7.11-7.03 (m, 1H, Aromatic), 6.98-6.91 (m, 1H, Aromatic) ppm; 13C NMR (75 MHz, CDC13) ö 159.4, 147.9, 144.5, 138.9, 126.7,118.9, 74.1, 26.6 ppm; JR (CHC13) v 2954, 1522 cm-i ESIMS: mlz (percent) 205 [M+j. Analysis calculated for C8H6F3N02 C 46.84, H 2.95, N 6.83. Found C 46.29, H 2.79, N 6.79. With sodium tetrahydroborate, isopropyl alcohol in chloroform, Time= 0.5h, T= 27 °C Patent; COUNCIL OF SCIENTIFIC and INDUSTRIAL RESEARCH; BARUA, Nabin Chandra; SAIKIA, Bishwajit; BORAH, Preetismita; BAISHYA, Gakul; WO2015/189862; (2015); (A1) English View in Reaxys

O N

Rx-ID: 368691 View in Reaxys 160/375 Yield

Conditions & References With methanol, palladium on activated charcoal, T= 20 °C , p= 14710.2Torr , Hydrogenation Patent; Comm. Solv. Corp.; US2483201; (1945) View in Reaxys

O N

Rx-ID: 25770579 View in Reaxys 161/375 Yield 26 %

Conditions & References 70.1.2 :To an acetic acid (5.7 mL) and dimethyl sulfoxide (95 mL) solution of 1-butyl-4-((E)-2-nitro-vinyl)-benzene (5.7 g, 27.8 mmol) described in Manufacturing Example 70-1-1 was added sodium borohydride (1.68 g, 44.5 mmol) at room temperature while cooling appropriately. This mixture was stirred for 3 hours at room temperature. The mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-2:1) to obtain the title compound (1.48 g, 26percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 0.90-0.94 (3H, m), 1.31-1.37 (2H, m), 1.54-1.61 (2H, m), 2.56-2.60 (2H, m), 3.27-3.30 (2H, m), 4.57-4.61 (2H, m), 7.10-7.15 (4H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 3h, T= 20 °C

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Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys O N

N N

Rx-ID: 11098386 View in Reaxys 162/375 Yield

Conditions & References

51 %

O N

H 2N

N O

Rx-ID: 3391074 View in Reaxys 163/375 Yield 64 % Chromat., 76 % 76 %, 64 % Chromat.

O N

O O

Rx-ID: 33657769 View in Reaxys 164/375 Yield 91 %

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N O

Rx-ID: 30033499 View in Reaxys 165/375 Yield

Conditions & References

75 %

With sodium tetrahydroborate in methanol, dichloromethane, Time= 0.833333h, T= 0 °C Chang, Chia-Fu; Huang, Chu-Yun; Huang, Yu-Chao; Lin, Kuan-Yu; Lee, Yean-Jang; Wang, Chau-Jong; Synthetic Communications; vol. 40; nb. 23; (2010); p. 3452 - 3466 View in Reaxys O

Rx-ID: 38266814 View in Reaxys 166/375 Yield

O O

(-)-enantiomer,rel-configuration

(+)-enantiomer,rel-configuration

Rx-ID: 38266815 View in Reaxys 167/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 83 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O N

Rx-ID: 38266816 View in Reaxys 168/375 Yield

O N

O O

(+)-enantiomer,rel-configuration

(-)-enantiomer,rel-configuration

Rx-ID: 38266817 View in Reaxys 169/375

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Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 55 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys O N

O N

NH 2

Rx-ID: 40573299 View in Reaxys 170/375 Yield

O N

NH 2

N O

Rx-ID: 2120301 View in Reaxys 171/375 Yield

Conditions & References

24 %, 16 %

in water, Time= 52h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

16 %, 24 %

in water, Time= 52h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys O

O O

N O

NH 2 N

Rx-ID: 2139095 View in Reaxys 172/375 Yield 61 %, 24 %

Conditions & References in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

24 %, 61 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

NH 2

Rx-ID: 2153487 View in Reaxys 173/375

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Yield

Conditions & References

28 %, 10 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

10 %, 28 %

in water, Time= 72h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys O

O N

O O

N N

Rx-ID: 4770756 View in Reaxys 174/375 Yield

Conditions & References

30 %

With yeast, water in Petroleum ether, Time= 24h, Ambient temperature Bak, Radoslaw R.; McAnda, Anita F.; Smallridge, Andrew J.; Trewhella, Maurie A.; Australian Journal of Chemistry; vol. 49; nb. 11; (1996); p. 1257 - 1260 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys O

N N

O O

N N

Rx-ID: 11098389 View in Reaxys 175/375 Yield

Conditions & References

88 %

36 %

O O N O

N O

O (+)-enantiomer,rel-configuration

(-)-enantiomer,rel-configuration

Rx-ID: 38266805 View in Reaxys 176/375 Yield

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Rx-ID: 1076484 View in Reaxys 177/375 Yield 86 %

Conditions & References With zinc(II) tetrahydroborate in DME, Time= 10h, T= 0 - 5 °C Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

86 %

With zinc(II) tetrahydroborate in DME, Time= 10h, T= 0 °C Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys

84 %

78 %

With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, Time= 24h, T= 100 °C , neat (no solvent) Chauhan, Pankaj; Kaur, Kirandeep; Bala, Neeraj; Kumar, Vikas; Chimni, Swapandeep Singh; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 50; nb. 3; (2011); p. 304 - 309 View in Reaxys

77 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 4h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

70 %

With sodium tetrahydroborate in methanol, dichloromethane, Time= 0.5h, T= 0 °C Chang, Chia-Fu; Huang, Chu-Yun; Huang, Yu-Chao; Lin, Kuan-Yu; Lee, Yean-Jang; Wang, Chau-Jong; Synthetic Communications; vol. 40; nb. 23; (2010); p. 3452 - 3466 View in Reaxys With hydrogenchloride, sodium cyanoborohydride in ethanol Seebach,D. et al.; Chemische Berichte; vol. 112; (1979); p. 234 - 248 View in Reaxys With sodium tetrahydroborate, hydrogen, Rh catalyst in N,N-dimethyl-formamide Love,C.J.; McQuillin,F.J.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1973); p. 2509 - 2512 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, Time= 2h, Reflux

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Wang, Yan-Xiang; Wang, Yu-Ping; Zhang, Hao; Kong, Wei-Jia; Li, Ying-Hong; Liu, Fei; Gao, Rong-Mei; Liu, Ting; Jiang, Jian-Dong; Song, Dan-Qing; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 21; (2009); p. 6004 - 6008 View in Reaxys 1.44 g

With sodium tetrahydroborate in methanol, dichloromethane, Time= 0.5h, T= 0 °C , Inert atmosphere, Schlenk technique Reddy, Golipalli Ramana; Mukherjee, Debopreeti; Chittoory, Arjun Kumar; Rajaram, Sridhar; Organic Letters; vol. 16; nb. 22; (2014); p. 5874 - 5877 View in Reaxys O

O N

Rx-ID: 1113342 View in Reaxys 178/375 Yield

Conditions & References With hydrogen, Wilkinson's catalyst Patent; Boehringer u.Sohn; FR2247221; (1975) French; DE2351027; (1975); ; vol. 83; nb. 96708; (1975) View in Reaxys

O O

Rx-ID: 1798739 View in Reaxys 179/375 Yield

Conditions & References

69 %

With sodium tetrahydroborate in tetrahydrofuran, methanol, Ambient temperature Kabalka, George W.; Laila Guindi; Varma, Rajender S.; Tetrahedron; vol. 46; nb. 21; (1990); p. 7443 - 7457 View in Reaxys

69 %

With sodium tetrahydroborate in tetrahydrofuran, methanol, Time= 0.666667h, Ambient temperature Varma, Rajender S.; Kabalka, George W.; Synthetic Communications; vol. 15; nb. 2; (1985); p. 151 - 156 View in Reaxys With silica gel, L-Selectridereg;, 1.) THF, RT, 30 min, Yield given. Multistep reaction Varma, Rajender S.; Kabalka, George W.; Synthetic Communications; vol. 14; nb. 12; (1984); p. 1093 - 1098 View in Reaxys

O E

Rx-ID: 1798933 View in Reaxys 180/375 Yield 92 %

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.5h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

82 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys

78 %

With sodium tetrahydroborate in ethanol, Time= 3h, T= 0 - 20 °C

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Preshlock, Sean; Calderwood, Samuel; Verhoog, Stefan; Tredwell, Matthew; Huiban, Mickael; Hienzsch, Antje; Gruber, Stefan; Wilson, Thomas C.; Taylor, Nicholas J.; Cailly, Thomas; Schedler, Michael; Collier, Thomas Lee; Passchier, Jan; Smits, René; Mollitor, Jan; Hoepping, Alexander; Mueller, Marco; Genicot, Christophe; Mercier, Joël; Gouverneur, Véronique; Chemical Communications; vol. 52; nb. 54; (2016); p. 8361 8364 View in Reaxys With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.25h, T= 25 °C Kodukulla; Trivedi; Vora; Mathur; Synthetic Communications; vol. 24; nb. 6; (1994); p. 819 - 832 View in Reaxys 2.A : (Intermediates of Formula 4) (A) A mixture of 3,4-dimethoxy-β-nitrostyrene (3, 140 g, 0.67 mol) 3° C.), methylene chloride (3.2 L), and isopropanol (2.0 L) was cooled to 5° C. and treated with silica gel (1.32 Kg, 70-230 mesh, EM Reagents). After stirring at 5° C. for 20 minutes, NaBH4 (88.6 g, 2.34 mol, Alfa Chemicals) was added over 30 minutes, followed by another 30 minutes of stirring at 5° C. The reaction was then quenched by adding 10percent aqueous HCl (280 mL). THe silica gel was filtered off and washed with CH2 Cl2 (2*150 mL). The combined filtrates were washed with water (1.0 L) followed by brine (1.0 L). The organic layer was removed in vacuo to yield 2-(3,4-dimethoxyphenyl)-1-nitroethane (4, 132 g, m.p. 50°-52° C.) as a pale yellow oil which solidified on standing. With hydrogenchloride, sodium tetrahydroborate in dichloromethane, isopropyl alcohol Patent; Syntex (U.S.A.) Inc.; US4667038; (1987); (A1) English View in Reaxys

N O

O O

N O

O O

Rx-ID: 2093084 View in Reaxys 181/375 Yield

Conditions & References

94 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.5h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

71 %

O O

E N

N O

Rx-ID: 2656260 View in Reaxys 182/375 Yield 90 %

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.25h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

80 %

Synthesis of 2-(3,5-dimethoxyphenyl) nitroethane (8) NaBH4 (0.5 g, 14 mmol) was added portion-wise at 20 °C to a solutionof 7 (2.0 g, 10 mmol) in ethyl acetate–ethanol (20 mL, 8 : 2 mmol).The contents were then stirred at room temperature for 2 h and the reaction was monitored by TLC. Usual work up followed by column chromatographic purification over silica gel provided, 1,3-dimethoxy-5-(2nitroethyl)benzene 8 as a reddish oil. Yield 1.6 g, (80percent);

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With sodium tetrahydroborate in ethanol, ethyl acetate, Time= 2h, T= 20 °C Limaye, Rohan A.; Joseph, Augustine R.; Natu, Arun D.; Paradkar, Madhusudan V.; Journal of Chemical Research; vol. 39; nb. 4; (2015); p. 191 - 194 View in Reaxys 7.B : 1-(2-Nitroethyl)-3,5-dimethoxybenzene Step B 1-(2-Nitroethyl)-3,5-dimethoxybenzene To a well stirred suspension of sodium borohydride (5 g) in a mixture of dioxane (100 ml) and absolute ethanol (30 ml) was added dropwise a solution of 1-(2-nitroethenyl)-3,5-dimethoxybenzene (12.6 g) in dioxane (100 ml) over a 1 hour period. Following addition the mixture was stirred for an additionnal 45 minutes period. To the resulting suspension were added ice-water (120 ml) and 50percent aqueous acetic acid (10 ml). Agitation was maintained for 1 hour and the clear solution was concentrated under reduced pressure. The residue was extracted with ethyl acetate/water, the organic layer was washed with saturated aqueous sodium chloride and dried over magnesium sulfate. Evaporation of solvents afforded the crude title compound (10.8 g). Trap to trap distillation under high vacuum (0.05 Millibars) at 180° C. yielded 1-(2-nitroethyl)-3,5-dimethoxybenzene as a colorless oil (6.8 g). With sodium borohydride, acetic acid in 1,4-dioxane, ice-water, ethanol Patent; Merrell Dow Pharmaceuticals Inc.; US5041673; (1991); (A1) English View in Reaxys

Rx-ID: 3965520 View in Reaxys 183/375 Yield

Conditions & References

85 %

Rx-ID: 35620430 View in Reaxys 184/375 Yield

Conditions & References

> 95 %Spectr.

F N

N F

Rx-ID: 9688228 View in Reaxys 185/375 Yield

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol

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Malancona, Savina; Colarusso, Stefania; Ontoria, Jesus M.; Marchetti, Antonella; Poma, Marco; Stansfield, Ian; Laufer, Ralph; Di Marco, Annalise; Taliani, Marina; Verdirame, Maria; Gonzalez-Paz, Odalys; Matassa, Victor G.; Narjes, Frank; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 17; (2004); p. 4575 - 4579 View in Reaxys

N O

N OH

Rx-ID: 10407246 View in Reaxys 186/375 Yield

Conditions & References

88 %

With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, T= 20 °C Zhang, Bang-Le; Wang, Fang-Dao; Yue, Jian-Min; Synlett; nb. 4; (2006); p. 567 - 570 View in Reaxys O

O O

Rx-ID: 38266812 View in Reaxys 187/375 Yield

O Cl

(-)-enantiomer,rel-configuration

(+)-enantiomer,rel-configuration

Rx-ID: 38266813 View in Reaxys 188/375 Yield

Rx-ID: 38266807 View in Reaxys 189/375 Yield

N O

(+)-enantiomer,rel-configuration

(-)-enantiomer,rel-configuration

Rx-ID: 38266808 View in Reaxys 190/375

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Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 86 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys O N

O N

NH 2

Rx-ID: 34059497 View in Reaxys 191/375 Yield

Conditions & References Reaction Steps: 2 1: sodium tetrahydroborate / methanol / 1.5 h / 20 °C / |Inert atmosphere 2: 10 Pd/C; hydrogen / methanol / |Inert atmosphere With sodium tetrahydroborate, 10 Pd/C, hydrogen in methanol Anderson, James C.; Noble, Adam; Torres, Pascual Ribelles; Tetrahedron Letters; vol. 53; nb. 42; (2012); p. 5707 - 5710 View in Reaxys H

H 13C O

13C

H O

13C

H 13C

13C

H O

N O

13C

N O

Rx-ID: 38014839 View in Reaxys 192/375 Yield

Conditions & References With sodium tetrahydroborate, ethanol in ethyl acetate, Time= 1h, T= 22 °C Karlsen, Morten; Liu, Huiling; Berg, Thomas; Johansen, Jon Eigill; Hoff, Bard Helge; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 57; nb. 5; (2014); p. 378 - 387 View in Reaxys

HO E

Rx-ID: 2553249 View in Reaxys 193/375 Yield

Conditions & References

73 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys

O O

HO O

Rx-ID: 28891700 View in Reaxys 194/375 Yield 71 %

Conditions & References With sodium tetrahydroborate in tetrahydrofuran, methanol

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Nunes, Rui M. D.; Pineiro, Marta; Arnaut, Luis G.; Journal of the American Chemical Society; vol. 131; nb. 26; (2009); p. 9456 - 9462 View in Reaxys O

F F

Rx-ID: 31039055 View in Reaxys 195/375 Yield

Conditions & References

737 mg

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 15.5h, T= 20 °C , Inert atmosphere Burkhard, Johannes A.; Tchitchanov, Boris H.; Carreira, Erick M.; Angewandte Chemie - International Edition; vol. 50; nb. 23; (2011); p. 5379 - 5382 View in Reaxys O

O N

Rx-ID: 2106454 View in Reaxys 196/375 Yield

Conditions & References

90 %

With anhydrous magnesium perchlorate, "grafted NADH model" reagent in acetonitrile, benzene, Time= 120h, T= 80 °C Trefouel, Thierry; Tintillier, Patrik; Dupas, Georges; Bourguignon, Jean; Queguiner, Guy; Bulletin of the Chemical Society of Japan; vol. 60; nb. 12; (1987); p. 4492 - 4494 View in Reaxys

O N

Rx-ID: 11220513 View in Reaxys 197/375 Yield

Conditions & References

82 %

O N

O Cl

Rx-ID: 11220514 View in Reaxys 198/375 Yield

Conditions & References

89 %

O N

Cl Cl

Rx-ID: 30361859 View in Reaxys 199/375

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Yield

Conditions & References

83 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 3h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

80 %

O O

Rx-ID: 35620431 View in Reaxys 200/375 Yield 95 %Spectr.

Conditions & References With 2,6-dimethylpyridine, C18H9BF6*C4H8O, hydrogen in dichloromethane-d2, Time= 24h, T= -196.16 - 40 °C , p= 3000.3Torr , Inert atmosphere, Schlenk technique, Glovebox Greb, Lutz; Daniliuc, Constantin-Gabriel; Bergander, Klaus; Paradies, Jan; Angewandte Chemie - International Edition; vol. 52; nb. 22; (2013); p. 5876 - 5879; Angew. Chem.; vol. 125; nb. 22; (2013); p. 5989 - 5992,4 View in Reaxys

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E N

Rx-ID: 25770572 View in Reaxys 201/375 Yield

Conditions & References

59 %

66.1.3 :To an acetic acid (3.7 mL) and dimethyl sulfoxide (63 mL) solution of 1-cyclopropylmethoxy-3-((E)-2-nitrovinyl)-benzene (3.73 g, 17 mmol) described in Manufacturing Example 66-1-2 was added sodium borohydride (1.03 g, 27.2 mmol) at room temperature while cooling appropriately. This mixture was stirred for 4 hours at room temperature. That mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1) to obtain the title compound (2.21 g, 59percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 0.30-0.32 (2H, m), 0.54-0.57 (2H, m), 1.17-1.24 (1H, m), 3.17-3.19 (2H, m), 3.78-3.80 (2H, m), 4.82-4.85 (2H, m), 6.77-6.82 (2H, m), 6.85-6.86 (1H, m), 7.17-7.21 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 4h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

Rx-ID: 25760810 View in Reaxys 202/375 Yield

Conditions & References

58 %

65.1.3 :To an acetic acid (3.9 mL) and dimethyl sulfoxide (67 mL) solution of 1-butoxy-3-((E)-2-nitro-vinyl)-benzene (3.92 g, 17.7 mmol) described in Manufacturing Example 65-1-2 was added sodium borohydride (1.07 g, 28.3 mmol) at room temperature while cooling appropriately. This mixture was stirred for 4 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1) to obtain the title compound (2.29 g, 58percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 0.91-0.95 (3H, m), 1.38-1.47 (2H, m), 1.65-1.70 (2H, m), 3.16-3.20 (2H, m), 3.92-3.95 (2H, m), 4.82-4.86 (2H, m), 6.78-6.82 (2H, m), 6.85-6.86 (1H, m), 7.18-7.22 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 4h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

Rx-ID: 25764682 View in Reaxys 203/375 Yield 76 %

Conditions & References 67.1.3 :To an acetic acid (4.4 mL) and dimethyl sulfoxide (75 mL) solution of 1-butoxy-4-((E)-2-nitro-vinyl)-benzene (4.44 g, 20.1 mmol) described in Manufacturing Example 67-1-2 was added sodium borohydride (1.22 g, 32.2 mmol) at room temperature while cooling appropriately. This mixture was stirred for 4 hours at room temperature. The mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1) to obtain the title compound (3.42 g, 76percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 0.90-0.95 (3H, m), 1.37-1.47 (2H, m), 1.63-1.70 (2H, m), 3.12-3.16 (2H, m), 3.91-3.94 (2H, m), 4.76-4.80 (2H, m), 6.83-6.87 (2H, m), 7.14-7.18 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 4h, T= 20 °C

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Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys O

Rx-ID: 38534469 View in Reaxys 204/375 Yield

Conditions & References

627 mg

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 2h, T= 20 °C , Inert atmosphere McLaughlin, Martin; Yazaki, Ryo; Fessard, Thomas C.; Carreira, Erick M.; Organic Letters; vol. 16; nb. 16; (2014); p. 4070 - 4073 View in Reaxys

O N

Rx-ID: 8753312 View in Reaxys 205/375 Yield

Conditions & References

92 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.666667h Kilway, Kathleen V; Siegel, Jay S; Tetrahedron; vol. 57; nb. 17; (2001); p. 3615 - 3627 View in Reaxys

O N

H 2N

O N

Rx-ID: 3390962 View in Reaxys 206/375 Yield

Conditions & References

69 % Chromat., 97 % 97 %, 69 % Chromat.

in ethanol, Heating Itoh, Kazuyoshi; Ishida, Hideaki; Chikashita, Hidenori; Chemistry Letters; (1982); p. 1117 - 1118 View in Reaxys in ethanol, Heating Itoh, Kazuyoshi; Ishida, Hideaki; Chikashita, Hidenori; Chemistry Letters; (1982); p. 1117 - 1118 View in Reaxys

O N

Rx-ID: 965493 View in Reaxys 207/375 Yield

Conditions & References With sodium tetrahydroborate Bailey,K. et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 3143 - 3151 View in Reaxys O O

Rx-ID: 2153719 View in Reaxys 208/375

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Yield

Conditions & References

70 %

With sodium tetrahydroborate in methanol, Time= 1h, Ambient temperature Rastogi, Shri Niwas; Kansal, V. K.; Bhaduri, A. P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 3; (1983); p. 234 - 237 View in Reaxys

O N

Rx-ID: 4309581 View in Reaxys 209/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane Coutts; Malicky; Canadian Journal of Chemistry; vol. 51; nb. 9; (1973); p. 1402 - 1409 View in Reaxys

O O

Rx-ID: 8869467 View in Reaxys 210/375 Yield

Conditions & References

70 %

With sodium tetrahydroborate in methanol, Time= 1h, T= 20 °C El Hadri; Nicolle; Guillaume; Leclerc; Pietri-Rouxel; Strosberg; Archimbault; Pharmazie; vol. 56; nb. 7; (2001); p. 517 - 522 View in Reaxys

O O

O E

Rx-ID: 38266872 View in Reaxys 211/375 Yield

O O

O (+)-enantiomer,rel-configuration

(-)-enantiomer,rel-configuration

Rx-ID: 38266873 View in Reaxys 212/375 Yield

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H N

N O N

Rx-ID: 11123782 View in Reaxys 213/375 Yield

Conditions & References

97.1 % Chromat.

With hydrogen, gold, Titanium(IV) oxide, Time= 2h, T= 90 °C , p= 7500.75Torr , Product distribution, Further Variations: Catalysts Corma, Avelino; Serna, Pedro; Garcia, Hermenegildo; Journal of the American Chemical Society; vol. 129; nb. 20; (2007); p. 6358 - 6359 View in Reaxys

O O

Rx-ID: 30636181 View in Reaxys 214/375 Yield

Conditions & References Reaction Steps: 3 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: nitric acid; acetic acid / 5 - 20 °C 3: dimethylsulfide borane complex / chloroform / 24 h / 20 °C With sodium tetrahydroborate, dimethylsulfide borane complex, nitric acid, acetic acid, sodium hydroxide in ethanol, chloroform Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

O O

N O

O N H 2N

Rx-ID: 16786499 View in Reaxys 215/375 Yield

Conditions & References Reaction Steps: 2 1: 90 percent / NaBH4, silica gel 2: cyclohexene / 10percent Pd/C / ethanol / Heating With sodium tetrahydroborate, silica gel, cyclohexene, palladium on activated charcoal in ethanol Maryanoff, Bruce E.; McComsey, David F.; Martin, Gregory E.; Shank, Richard P.; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 8; (1998); p. 983 - 988 View in Reaxys Reaction Steps: 2 1: 92 percent / sodium borohydride / methanol; ethyl acetate / 0.25 h / 0 °C 2: 95 percent / hydrogen / PtO2 / acetic acid / 3 h / 760 Torr / Ambient temperature With sodium tetrahydroborate, hydrogen, platinum(IV) oxide in methanol, acetic acid, ethyl acetate Andrew, Robert G.; Raphael, Ralph A.; Tetrahedron; vol. 43; nb. 21; (1987); p. 4803 - 4816 View in Reaxys

O O

N 2H

Rx-ID: 30636167 View in Reaxys 216/375

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Yield

Conditions & References Reaction Steps: 4 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: pyridine; methanol-d4 / 35 h / Reflux; Inert atmosphere 3: nitric acid; acetic acid / 5 - 20 °C 4: dimethylsulfide borane complex / chloroform / 24 h / 20 °C With pyridine, sodium tetrahydroborate, methanol-d4, dimethylsulfide borane complex, nitric acid, acetic acid, sodium hydroxide in ethanol, chloroform Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

O O

Rx-ID: 25915504 View in Reaxys 217/375 Yield 56.2 %

Conditions & References 353 :1-Fluoro-3-(2-nitro-ethyl)-5-propoxy-benzene Add sodium borohydride (1.30 g, 34.46 mmol) to 1-fluoro-3-((E)-2-nitro-vinyl)-5-propoxy-benzene (1.94 g, 8.61 mmol) and silica gel (17 g) in chloroform (86 mL) and isopropanol (25 mL) at room temperature in portions over 5 minutes. Stir at room temperature 2 hours and filter. Concentrate the filtrate and dissolve in ethyl acetate. Wash with water and saturated aqueous sodium chloride, dry over magnesium sulfate, filter and concentrate. Purify on 40 g silica gel eluding with 100:0 to 70:30 hexanes:ethyl acetate to give 1.1 g (56.2percent) of the desired compound as an oil. 1H-NMR (400 MHz, CDCl ) δ 6.53-6.47 (m, 3H), 4.59 (t, 2H, J=7.3 Hz), 3.88 (t, 2H, J=6.6 Hz), 3.26 (t, 2H, J=7.5 Hz), 3 1.84-1.75 (m, 2H), 1.03 (t, 3H, J=7.5 Hz). With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 2h, T= 20 °C Patent; Broughton, Howard Barff; Dally, Robert Dean; Durham, Timothy Barrett; Gonzalez-Garcia, Maria Rosario; Sa, Lilly; Hahn, Patric James; Henry, Kenneth James; Kohn, Todd Jonathan; McCarthy, James Ray; Shepherd, Timothy Alan; Erickson, Jon Andre; Bueno Melendo, Ana Belen; US2007/225267; (2007); (A1) English View in Reaxys

N O

Rx-ID: 4566310 View in Reaxys 218/375 Yield 87 %

Conditions & References With sodium tetrahydroborate in ethanol, Time= 0.75h, T= 30 °C Tarnus, Celine; Remy, Jean-Marc; D'Orchymont, Hugues; Bioorganic and Medicinal Chemistry; vol. 4; nb. 8; (1996); p. 1287 - 1297 View in Reaxys

O O

Rx-ID: 25775035 View in Reaxys 219/375

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Yield

Conditions & References 85.1.2 :To a mixture of 3-phenyl-benzaldehyde (430 mg, 2.4 mmol) described in Manufacturing Example 85-1-1 and acetic acid (7 mL) were added nitromethane (0.95 mL, 18 mmol) and ammonium acetate (540 mg, 7.1 mmol), which was stirred for 2.5 hours at 100° C. The reaction mixture was cooled to room temperature, and water was added at the same temperature, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. A mixture of dimethyl sulfoxide (9.3 mL) and acetic acid (0.62 mL) was added to the resulting residue, and sodium borohydride (140 mg, 3.8 mmol) was added to the reaction mixture at room temperature while cooling appropriately. The reaction mixture was stirred for 10 minutes at the same temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The resulting residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain the title compound (380 mg, 71percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.39 (2H, t, J=7.4 Hz), 4.64-4.68 (2H, m), 7.18-7.20 (1H, m), 7.34-7.52 (6H, m), 7.55-7.57 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

N O

Rx-ID: 45396040 View in Reaxys 220/375 Yield

Conditions & References

1.c :To a solution of compound 3 (10 g, 44.4 mmol) in dimethylsine (35 mL) at 0 ° C(5 mL, 88.8 mmol) was added to the solution, followed by addition of sodium borohydride (0.51G, 13.3 mmol) and stirred for 90 min. The reaction process was monitored by TLC. The reaction mixture was addedWas quenched with ice-cold water (50 mL) at 0 ° C and extracted with dichloromethane (2 χ 100 mL).The combined organic layers were washed with water (2 χ 100 mL) and saturated saline solution (100 mL)Dried Na2S04 dried and concentrated under reduced pressure. The crude material is analyzed by column chromatography on silica gelPurification was carried out using 6percent ethyl acetate in hexanes as a solution to give a solution which was a pale yellow solidCompound 4. Yield: 6 g (26.4 mmol, 34percent over 3 steps). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 0 °C Patent; NOVARTIS AG; MARTIN, BENJAMIN; MANDRELLI, FRANCESCA; VENTURONI, FRANCESCO; (106 pag.); TW2016/32493; (2016); (A) Chinese View in Reaxys

O N

O O

Rx-ID: 25775034 View in Reaxys 221/375 Yield

Conditions & References 84.1.2 :To a mixture of 3-pyridin-2-yl-benzaldehyde (290 mg, 1.6 mmol) described in Manufacturing Example 84-1-1 and acetic acid (5 mL) were added nitromethane (0.65 mL, 12 mmol) and ammonium acetate (370 mg, 4.8 mmol), which was stirred for 2 hours at 100° C. The reaction mixture was cooled to room temperature and water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. A mixture of dimethyl sulfoxide (6 mL) and acetic acid (0.4 mL) was added to the resulting residue, and sodium borohydride (97 mg, 2.6 mmol) was added at room temperature while cooling appropriately. The reaction mixture was stirred for 10 minutes at the same temperature. Water was added to the reaction mixture at room temperature, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The resulting residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (260 mg, 71percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.41 (2H, t, J=7.5 Hz), 4.67 (2H, t, J=7.5 Hz), 7.24-7.27 (2H, m), 7.44 (1H, t, J=7.7 Hz), 7.70-7.79 (2H, m), 7.85 (1H, d, J=7.9 Hz), 7.90 (1H, s), 8.68-8.70 (1H, m).

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With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

H 2N

NH Cl N

H 2N

Cl N

Rx-ID: 3391013 View in Reaxys 222/375 Yield

Conditions & References

81 % Chromat., 95 % 95 %, 81 % Chromat.

O O

Rx-ID: 43070137 View in Reaxys 223/375 Yield

Conditions & References

64 %

With sodium tetrahydroborate in ethanol, Time= 3h, T= 0 - 20 °C Preshlock, Sean; Calderwood, Samuel; Verhoog, Stefan; Tredwell, Matthew; Huiban, Mickael; Hienzsch, Antje; Gruber, Stefan; Wilson, Thomas C.; Taylor, Nicholas J.; Cailly, Thomas; Schedler, Michael; Collier, Thomas Lee; Passchier, Jan; Smits, René; Mollitor, Jan; Hoepping, Alexander; Mueller, Marco; Genicot, Christophe; Mercier, Joël; Gouverneur, Véronique; Chemical Communications; vol. 52; nb. 54; (2016); p. 8361 8364 View in Reaxys

Rx-ID: 2142370 View in Reaxys 224/375 Yield

Conditions & References

61 %

in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

O N

Br N

Rx-ID: 2147722 View in Reaxys 225/375 Yield 79 %

Conditions & References With (3,5-(CF3)2C6H3NH)2C=S, 2,6-di(Me)-1,4-dihydropyridine-3,5-di(COOEt) in dichloromethane, Time= 24h, Heating Zhang, Zhiguo; Schreiner, Peter R.; Synthesis; nb. 16; (2007); p. 2559 - 2564 View in Reaxys

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46 %

in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

O N

O Br

Rx-ID: 3250023 View in Reaxys 226/375 Yield 52 %

Conditions & References in water, Time= 74h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Rx-ID: 30033506 View in Reaxys 227/375 Yield 96 %

Conditions & References With 1,4-diaza-bicyclo[2.2.2]octane, tris(2,4,6-trifluorophenyl)borane, Time= 24h, T= 50 °C , p= 3750.38Torr , Inert atmosphere Nicasio, Juan A.; Steinberg, Sebastian; Ines, Blanca; Alcarazo, Manuel; Chemistry - A European Journal; vol. 19; nb. 33; (2013); p. 11016 - 11020 View in Reaxys

94 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, [(η5-C5Me5)2Rh2(μ-Cl)2Cl2], triethylamine, N-(2-amino-ethyl)-4-methyl-benzenesulphonamide in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

67 %

N O

Br N

Rx-ID: 30361848 View in Reaxys 228/375 Yield 93 %

Conditions & References With hantzsch ester in water, Time= 24h, T= 100 °C , Green chemistry, chemoselective reaction He, Qi; Xu, Zhihong; Jiang, Dehong; Ai, Wensi; Shi, Ronghua; Qian, Shan; Wang, Zhouyu; RSC Advances; vol. 4; nb. 17; (2014); p. 8671 - 8674

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View in Reaxys 90 %

4.2. General procedure for the transfer hydrogenation of conjugated nitroalkenes General procedure: A mixture of the TsEN ligand (0.0044 mmol), [RhCl2Cp*]2 (0.002 mmol), and triethylamine (11 μL, 0.08 mmol) was dissolved in1 mL methanol and heated at 70 °C for 1 h in a glass tube. After cooling down, the solvent was removed in vacuo. Nitroalkene substrate (0.4 mmol) in EtOAc (1.0 mL) and the azeotrope of formic acid/ triethylamine (0.2 mL) were added in turn. The mixture was stirred at 28 °C for the corresponding time. After completion, the solution was washed with water. The aqueous layer was extracted with EtOAc (5 mL.x.3). The combined organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 1h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys

75 %

4.2. Typical procedure for the reduction of conjugated nitroalkenes General procedure: The mixture of nitroalkenes 1 (0.1 g, 0.67 mmol), Hantzsch ester (0.19 g, 0.74 mmol) and Sbenzyl isothiouronium chloride (14 mg, 0.067 mmol) in methanol (5 ml) was stirred at 60 °C for 5-12 h. After completion of the reaction, the crude product in methanol was concentrated and added into the excess cooled CH2Cl2. The S-benzyl isothiouronium chloride was readily precipitated out, and then filtered and washed many times with CH2Cl2 to be reused. The filtrate was evaporated and the residue was purified by flash column chromatography to give the required nitroalkanes products 2. All nitroalkanes except 2j and 2p were characterized with the reported spectroscopic data. [2] and [5] With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, S-benzyl isothiouronium chloride in methanol, T= 60 °C , Inert atmosphere Nguyen, Quynh Pham Bao; Kim, Jae Nyoung; Kim, Taek Hyeon; Tetrahedron; vol. 68; nb. 32; (2012); p. 6513 6516 View in Reaxys 4.1.3. General procedure A: preparation of 1-aryl-1-nitroethanes General procedure: Sodium borohydride (15.00 mmol, 5.70 g) was added to a vigorously stirred mixture of the appropriate nitroethene (3.68 mmol), silica gel (9.30 g) and propan-2-ol (100 mL) in dichloromethane (350 mL) at room temperature. The mixture was stirred at room temperature for 20 min until the solution turned colourless. Excess NaBH4 was quenched with the addition of dilute HCl (50 mL). The mixture was filtered and the silica gel washed with dichloromethane (100 mL). All organic phases were combined and washed with brine (3 .x. 50 mL) and water (3 .x. 50 mL). The organic phases were then dried over anhydrous Mg2SO4 and the solvent removed in vacuo. The crude product was purified by column chromatography over silica gel. With sodium tetrahydroborate, silica gel in dichloromethane, isopropyl alcohol, Time= 0.333333h, T= 20 °C McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.; Keating, John J.; Butler, Stephen G.; Peters, Guenther H.; Meegan, Mary J.; Williams, D. Clive; Bioorganic and Medicinal Chemistry; vol. 19; nb. 3; (2011); p. 1328 - 1348 View in Reaxys

O O

O Br

Rx-ID: 33493016 View in Reaxys 229/375 Yield 88 %

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organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by flash chromatography (PE/EtOAc) on silica gel to provide the pure reduction product. With formic acid, dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer, triethylamine, N-tosylethylenediamine in ethyl acetate, Time= 15h, T= 28 °C , chemoselective reaction Xiang, Jing; Sun, Er-Xiao; Lian, Chun-Xia; Yuan, Wei-Cheng; Zhu, Jin; Wang, Qiwei; Deng, Jingen; Tetrahedron; vol. 68; nb. 24; (2012); p. 4609 - 4620 View in Reaxys 74 %

To a cold (0 °C) solution of Intermediate BH (2g, 8.77 mmol) in methanol(30 mL) at 0 °C was added NaBH4 (0.4g, 10.52 mmol) portionwise over 15 minutes. After the addition was complete, the reaction mixture was allowed to stir at 10 °C for 1 hour. The reaction mixture was quenched with water (10 mL) and concentrated under reduced pressure. The resulting aqueous residue was diluted with water (25 mL) and extracted with ethyl acetate (2 χ 50 mL). The combined ethyl acetate layers were washed with water (30 mL) and brine solution (25 mL), dried over anhydrous Na2S04, and the solvent was removed to afford the crude product. This material was purified by column chromatography (silica gel 100-200 mesh) using 5percent ethyl acetate in petroleum ether as the eluent to afford Intermediate Β (1.5 g, 74percent) as pale yellow solid. NMR (CDC13): δ 7.39 (d, J= 10.78 Hz, 1H), 7.37(s, 1H), 7.22-7.15 (m, 2H), 4.61 (t, J= 7.46 Hz, 2H), 3.29 (t, J= 7.03 Hz, 2H). Mass (M-2H), M: 227.9, 229.9. With sodium tetrahydroborate in methanol, Time= 1.25h, T= 0 - 10 °C Patent; HERCULES TECHNOLOGY MANAGEMENT CO V, INC.; BLAGG, Julian; WO2011/47156; (2011); (A1) English View in Reaxys O O

N O

Rx-ID: 40573295 View in Reaxys 230/375 Yield

Conditions & References With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate in neat (no solvent), T= 100 °C Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831 View in Reaxys O

O O

O N

N N

Rx-ID: 40573298 View in Reaxys 231/375 Yield

Conditions & References With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate in neat (no solvent), T= 100 °C Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831 View in Reaxys

O N

F N

N F

NH 2

Rx-ID: 40573302 View in Reaxys 232/375 Yield

Conditions & References Reaction Steps: 2 1: diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate / neat (no solvent) / 100 °C

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2: hydrogen; palladium on activated charcoal / methanol With diethyl-1,4-dihydro-2,6-dimethyl-3,5-pyridine dicarboxylate, palladium on activated charcoal, hydrogen in methanol Maity, Rajendra; Pan, Subhas Chandra; Organic and Biomolecular Chemistry; vol. 13; nb. 24; (2015); p. 6825 6831 View in Reaxys O N

O N

Rx-ID: 39669104 View in Reaxys 233/375 Yield

Conditions & References

86 %

With sodium tetrahydroborate in methanol, Time= 2h, T= 20 °C Patent; NORTHEASTERN UNIVERSITY; THAKUR, Ganeshsingh, Arjunsingh; TICHKULE, Ritesh, B.; KULKARNI, Pushkar, Mukund; KULKARNI, Abhijit, Raghunath; WO2015/27160; (2015); (A2) English View in Reaxys

Rx-ID: 41810146 View in Reaxys 234/375 Yield

Conditions & References

85 %

With sodium tetrahydroborate in methanol, Time= 2h, T= 5 - 20 °C , Inert atmosphere Kulkarni, Pushkar M.; Kulkarni, Abhijit R.; Korde, Anisha; Tichkule, Ritesh B.; Laprairie, Robert B.; DenovanWright, Eileen M.; Zhou, Han; Janero, David R.; Zvonok, Nikolai; Makriyannis, Alexandros; Cascio, Maria G.; Pertwee, Roger G.; Thakur, Ganesh A.; Journal of Medicinal Chemistry; vol. 59; nb. 1; (2016); p. 44 - 60 View in Reaxys

O N

Rx-ID: 25775031 View in Reaxys 235/375 Yield 68 %

Conditions & References 78.1.3 :To an acetic acid (4.8 mL) and dimethyl sulfoxide (82 mL) solution of 1-cyclopentyloxy-4-((E)-2-nitro-vinylbenzene (4.8 g, 20.4 mmol) described in Manufacturing Example 78-1-2 was added sodium borohydride (1.23 g, 32.6 mmol) at room temperature while cooling appropriately. The mixture was stirred for 1.5 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-2:1) to obtain the title compound (3.24 g, 68percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 1.59-1.65 (2H, m), 1.76-1.92 (6H, m), 3.23-3.27 (2H, m), 4.55-4.58 (2H, m), 4.70-4.74 (1H, m), 6.80-6.84 (2H, m), 7.07-7.11 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

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NH N

O O

NH N

Rx-ID: 4019879 View in Reaxys 236/375 Yield

Conditions & References With sodium tetrahydroborate in ethanol, Time= 5h, Yield given Florvall; Persson; Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry; vol. 36; nb. 3 B; (1982); p. 141 - 146 View in Reaxys

O O

N O

Rx-ID: 25775017 View in Reaxys 237/375 Yield

Conditions & References 4.1.3 :To a solution of 4-butoxymethyl-benzaldehyde (7.39 g, 3.84 mmol) described in Manufacturing Example 4-1-2 in methanol (140 mL) was added nitromethane (2.70 mL, 49.9 mmol) followed by sodium methoxide (1.49 M methanol solution, 9.41 mL, 46.1 mmol) at 0° C. The reaction solution was stirred for 30 minutes at room temperature, and 5 N aqueous hydrochloric acid solution (120 mL) was added thereto and stirred for further 25 minutes. This reaction solution was partitioned into saturated aqueous sodium chloride and ethyl acetate at 0° C. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. To a solution of the resulting residue in dimethyl sulfoxide (100 mL) and acetic acid (6 mL) was added sodium borohydride (1.84 g, 46.1 mmol) at room temperature while cooling appropriately. This solution was then stirred for 80 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1) to obtain the title compound (2.68 g, 29percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 0.918 (3H, t, J=7.3 Hz), 1.37-1.42 (2H, m), 1.56-1.63 (2H, m), 3.31 (2H, t, J=7.3 Hz), 3.47 (2H, t, J=6.6 Hz), 4.47 (2H, s), 4.60 (2H, t, J=7.3 Hz), 7.18 (2H, d, J=8.2 Hz), 7.30 (2H, d, J=8.2 Hz). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.33333h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O O

N O

Rx-ID: 45635807 View in Reaxys 238/375 Yield

Conditions & References Reaction Steps: 2 1: silica gel; sodium tetrahydroborate / isopropyl alcohol; chloroform 2: (2,9-dimethyl-4,7-diphenyl-1,10-phenantroline)NiBr2; diethylzinc; potassium tert-butylate / tert-butyl methyl ether; 1,4-dioxane / 24 h / 40 °C / Inert atmosphere; Sealed tube; Glovebox With sodium tetrahydroborate, (2,9-dimethyl-4,7-diphenyl-1,10-phenantroline)NiBr2, potassium tert-butylate, diethylzinc, silica gel in 1,4-dioxane, tert-butyl methyl ether, chloroform, isopropyl alcohol Rezazadeh, Sina; Devannah, Vijayarajan; Watson, Donald A.; Journal of the American Chemical Society; vol. 139; nb. 24; (2017); p. 8110 - 8113 View in Reaxys

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O N

Rx-ID: 40573301 View in Reaxys 239/375 Yield

O N

Rx-ID: 4306486 View in Reaxys 240/375 Yield

Conditions & References With sodium tetrahydroborate in tetrahydrofuran, ethanol Gal,J. et al.; Journal of Medicinal Chemistry; vol. 18; nb. 7; (1975); p. 683 - 688 View in Reaxys O

O O

Rx-ID: 37057632 View in Reaxys 241/375 Yield

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 4h, T= 0 - 25 °C Kimura, Shinya; Pangkruang, Waree; Yokoya, Masashi; Honda, Amane; Puthongking, Ploenthip; Suwanborirux, Khanit; Saito, Naoki; Heterocycles; vol. 88; nb. 1; (2014); p. 363 - 375 View in Reaxys

Rx-ID: 30636179 View in Reaxys 242/375 Yield

Conditions & References Reaction Steps: 2 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: nitric acid; acetic acid / 5 - 20 °C With sodium tetrahydroborate, nitric acid, acetic acid, sodium hydroxide in ethanol Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

N O

E F

F F

Rx-ID: 31039072 View in Reaxys 243/375

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Yield

Conditions & References

245 mg

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 15.5h, Inert atmosphere Burkhard, Johannes A.; Tchitchanov, Boris H.; Carreira, Erick M.; Angewandte Chemie - International Edition; vol. 50; nb. 23; (2011); p. 5379 - 5382 View in Reaxys

N 2H

Rx-ID: 30636180 View in Reaxys 244/375 Yield

Conditions & References Reaction Steps: 3 1: sodium tetrahydroborate; sodium hydroxide / ethanol / 1 h / 0 °C 2: pyridine; methanol-d4 / 35 h / Reflux; Inert atmosphere 3: nitric acid; acetic acid / 5 - 20 °C With pyridine, sodium tetrahydroborate, methanol-d4, nitric acid, acetic acid, sodium hydroxide in ethanol Backstroma, Nicholas; Burtona, Neil A.; Watta, C. Ian F.; Journal of Physical Organic Chemistry; vol. 23; nb. 8; (2010); p. 711 - 722 View in Reaxys

O O

N O

O N

Rx-ID: 1996304 View in Reaxys 245/375 Yield

Conditions & References

94 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.666667h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

O O

N O

Rx-ID: 2095911 View in Reaxys 246/375 Yield

Conditions & References

94 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.583333h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys

N O

Rx-ID: 2158767 View in Reaxys 247/375 Yield 94 %

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were added 4 mmol of NaBH4 per mmol of starting material in small amounts and the resulting mixture was allowed to stir at room temperature until the complete disappearance of the 2-aryl-1-nitroethene (usually noted after a reaction time of about 30 min). The reaction mixture was quenched with an aqueous solution of 0.1 N HCl, filtered to eliminate the silica gel and evaporated under vacuum to eliminate 2-propanol and chloroform. The resulting aqueous mixture was then extracted by CH2Cl2 (3.x.). The organic phase was dried over MgSO4, filtered and concentrated under vacuum. Crude product was purified by chromatography on silica gel in order to afford the desired compound. With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.5h, T= 20 °C Mur Blanch, Nuria; Chabot, Guy G.; Quentin, Lionel; Scherman, Daniel; Bourg, Stephane; Dauzonne, Daniel; European Journal of Medicinal Chemistry; vol. 54; (2012); p. 22 - 32 View in Reaxys 92.5 %

With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 2h Dauzonne; Royer; Chemical and Pharmaceutical Bulletin; vol. 34; nb. 4; (1986); p. 1628 - 1633 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, Time= 2h, Reflux Wang, Yan-Xiang; Wang, Yu-Ping; Zhang, Hao; Kong, Wei-Jia; Li, Ying-Hong; Liu, Fei; Gao, Rong-Mei; Liu, Ting; Jiang, Jian-Dong; Song, Dan-Qing; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 21; (2009); p. 6004 - 6008 View in Reaxys H N

H N O

N O

Rx-ID: 25770577 View in Reaxys 248/375 Yield

Conditions & References

62 %

69.1.3 :To an acetic acid (3.2 mL) and dimethyl sulfoxide (54 mL) solution of (4-((E)-2-nitro-vinyl)-phenyl)-phenylamine (3.2 g, 13.4 mmol) described in Manufacturing Example 69-1-2 was added sodium borohydride (811 mg, 21.4 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1 hour at room temperature. The mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-2:1) to obtain the title compound (2.01 g, 62percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.24-3.28 (2H, m), 4.56-4.60 (2H, m), 5.81 (1H, brs), 6.93-6.98 (1H, m), 7.00-7.12 (6H, m), 7.24-7.29 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

Rx-ID: 25769348 View in Reaxys 249/375 Yield 28 %

Conditions & References 17.1.3 :Manufacturing Example 17-1-3 1-(2-Nitro-ethyl)-4-phenoxy-benzene; To a solution of 1-((E)-2-nitro-vinyl)-4phenoxy-benzene (1.40 g, 2.90 mmol, purity: 50percent) described in Manufacturing Example 17-1-2 in methanol (15 mL) was added sodium borohydride (274 mg, 7.25 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (199 mg, 28percent).1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.21 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 6.94-7.00 (4H, m), 7.11-7.15 (1H, m), 7.28-7.30 (2H, m), 7.36-7.40 (2H, m).

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Stage 1: With sodium tetrahydroborate in methanol, Time= 0.166667h, T= 20 °C Stage 2: With water in methanol Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys 28 %

17.1.3 :To a solution of 1-((E)-2-nitro-vinyl)-4-phenoxy-benzene (1.40 g, 2.90 mmol, purity: 50percent) described in Manufacturing Example 17-1-2 in methanol (15 mL) was added sodium borohydride (274 mg, 7.25 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (199 mg, 28percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.21 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 6.94-7.00 (4H, m), 7.11-7.15 (1H, m), 7.28-7.30 (2H, m), 7.36-7.40 (2H, m). With sodium tetrahydroborate in methanol, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O O

Rx-ID: 25770569 View in Reaxys 250/375 Yield 68.1 %

Conditions & References 64.1.2 :To a dimethyl sulfoxide (30.0 mL) solution of 1-((E)-2-nitro-vinyl)-3-phenoxy-benzene (3.60 g, 14.9 mmol) described in Manufacturing Example 64-1-1 and acetic acid (3.00 mL) was added sodium borohydride (902 mg, 23.8 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 3 minutes. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduce pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (2.47 g, 68.1percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.22 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 6.85-6.88 (1H, m), 6.98-7.00 (3H, m), 7.04-7.06 (1H, m), 7.12-7.16 (1H, m), 7.30-7.34 (1H, m), 7.37-7.41 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.05h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

Br N

Rx-ID: 2070998 View in Reaxys 251/375 Yield 80 %

Conditions & References With borohydride supported ion exchange resin in methanol, Time= 1h, Ambient temperature Goudgaon, Naganna M.; Wadgaonkar, Prakash P.; Kabalka, George W.; Synthetic Communications; vol. 19; nb. 5and6; (1989); p. 805 - 812 View in Reaxys

O O

Rx-ID: 2153094 View in Reaxys 252/375

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Yield

Conditions & References

44 %

in water, Time= 70h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys

Rx-ID: 2153096 View in Reaxys 253/375 Yield

Conditions & References

52 %

in water, Time= 69h, T= 33 °C , baker's yeast Takeshita, Mitsuhiro; Yoshida, Sachiko; Kohno, Yoichiro; Heterocycles; vol. 37; nb. 1; (1994); p. 553 - 562 View in Reaxys With D-glucose, glucose dehydrogenase CDX901, ene reductase OPR1 from Lycopersicon escultentum, NADPH in aq. phosphate buffer, Time= 24h, T= 20 °C , pH= 7, Enzymatic reaction, Reagent/catalyst Reß, Tina; Hummel, Werner; Hanlon, Steven P.; Iding, Hans; Gröger, Harald; ChemCatChem; vol. 7; nb. 8; (2015); p. 1302 - 1311 View in Reaxys

Rx-ID: 36298024 View in Reaxys 254/375 Yield

Conditions & References

205 mg

With glucose dehydrogenase, D-Glucose, NADPH, citric acid in aq. phosphate buffer, ethanol, Time= 10h, T= 9 °C , pH= 6, Sonication, enantioselective reaction Burda, Edyta; Reß, Tina; Winkler, Till; Giese, Carolin; Kostrov, Xenia; Huber, Tobias; Hummel, Werner; Gröger, Harald; Angewandte Chemie - International Edition; vol. 52; nb. 35; (2013); p. 9323 - 9326; Angew. Chem.; vol. 125; nb. 35; (2013); p. 9493 - 9496 View in Reaxys

Br N

O N

Rx-ID: 36298027 View in Reaxys 255/375 Yield

O N O

Br N

Rx-ID: 38266802 View in Reaxys 256/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane, ethanol, T= 20 °C , Cooling with ice

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Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys

O N

Rx-ID: 38266803 View in Reaxys 257/375 Yield

Conditions & References With CyPF-PtBu, [Rh(norbornadiene)2]SbF6, hydrogen in dichloromethane, Time= 36h, T= 70 °C , p= 38002.6Torr , Autoclave, Overall yield = 91 percent; enantioselective reaction Li, Shengkun; Huang, Kexuan; Zhang, Xumu; Chemical Communications; vol. 50; nb. 64; (2014); p. 8878 - 8881 View in Reaxys With D-glucose, glucose dehydrogenase CDX901, ene reductase NCR from Zymomonas mobilis, NADPH, sodium hydroxide in isopropyl alcohol, Time= 66h, T= 9 °C , pH= 8, Enzymatic reaction, Catalytic behavior, Reagent/catalyst, Solvent, Overall yield = 34 percent; enantioselective reaction Reß, Tina; Hummel, Werner; Hanlon, Steven P.; Iding, Hans; Gröger, Harald; ChemCatChem; vol. 7; nb. 8; (2015); p. 1302 - 1311 View in Reaxys

O N

Rx-ID: 40126864 View in Reaxys 258/375 Yield

Conditions & References With D-glucose, glucose dehydrogenase CDX901, Ene-111 reductase, NADPH, sodium hydroxide in isopropyl alcohol, Time= 142.5h, T= 9 °C , pH= 6.2, Enzymatic reaction, enantioselective reaction Reß, Tina; Hummel, Werner; Hanlon, Steven P.; Iding, Hans; Gröger, Harald; ChemCatChem; vol. 7; nb. 8; (2015); p. 1302 - 1311 View in Reaxys

O N

Rx-ID: 25770589 View in Reaxys 259/375 Yield 40.6 %

Conditions & References 76.1.3 :To a dimethyl sulfoxide (15.0 mL) solution of 3-(4-((E)-2-nitro-vinyl)-phenoxy)-pyridine (2.00 g, 8.26 mmol) described in Manufacturing Example 76-1-2 and acetic acid (2.00 mL) was added sodium borohydride (500 mg, 13.2 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 30 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3-->1:2) to obtain the title compound (819 mg, 40.6percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.26 (2H, t, J=6.8 Hz), 4.88 (2H, t, J=6.8 Hz), 7.17 (2H, d, J=8.4 Hz), 7.40 (2H, d, J=8.4 Hz), 7.68-7.76 (2H, m), 8.23 (1H, s), 8.35 (1H, d, J=5.2 Hz). With sodium tetrahydroborate, acetic acid in dimethylsulfoxide-d6, Time= 0.5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

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F O

O O

N F

Rx-ID: 9688837 View in Reaxys 260/375 Yield

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol Malancona, Savina; Colarusso, Stefania; Ontoria, Jesus M.; Marchetti, Antonella; Poma, Marco; Stansfield, Ian; Laufer, Ralph; Di Marco, Annalise; Taliani, Marina; Verdirame, Maria; Gonzalez-Paz, Odalys; Matassa, Victor G.; Narjes, Frank; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 17; (2004); p. 4575 - 4579 View in Reaxys

O O

Rx-ID: 25770547 View in Reaxys 261/375 Yield

Conditions & References

77 %

46.1.5 :Manufacturing Example 46-1-5 2-Methyl-5-(4-(2-nitrothyl)-benzyl)-furan ; To a mixture of 2-methyl-5-(4((E)-2-nitro-vinyl)-benzyl)-furan (120 mg) described in Manufacturing Example 46-1-4, acetic acid (0.2 mL) and dimethyl sulfoxide (3.4 mL) was added sodium borohydride (29 mg, 0.77 mmol) at room temperature while cooling appropriately, which was stirred for 20 minutes at room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by neutral silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (90 mg, 77percent).1H-NMR Spectrum (CDCl3) δ (ppm): 2.24 (3H, s), 3.30 (2H, t, J=7.4 Hz), 3.89 (2H, s), 4.59 (2H, t, J=7.4 Hz), 5.85-5.87 (2H, m), 7.14 (2H, d, J=8.2 Hz), 7.20 (2H, d, J=8.2 Hz). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.333333h, T= 20 °C Stage 2: With water in dimethyl sulfoxide Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

77 %

46.1.5 :To a mixture of 2-methyl-5-(4-((E)-2-nitro-vinyl)-benzyl)-furan (120 mg) described in Manufacturing Example 46-1-4, acetic acid (0.2 mL) and dimethyl sulfoxide (3.4 mL) was added sodium borohydride (29 mg, 0.77 mmol) at room temperature while cooling appropriately, which was stirred for 20 minutes at room temperature. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by neutral silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (90 mg, 77percent). 1HNMR Spectrum (CDCl3) δ (ppm): 2.24 (3H, s), 3.30 (2H, t, J=7.4 Hz), 3.89 (2H, s), 4.59 (2H, t, J=7.4 Hz), 5.85-5.87 (2H, m), 7.14 (2H, d, J=8.2 Hz), 7.20 (2H, d, J=8.2 Hz). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.333333h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

Rx-ID: 25770600 View in Reaxys 262/375 Yield 53 %

Conditions & References 80.1.6 :To a mixed tetrahydrofuran-dimethyl sulfoxide (1:1, 10 mL) solution of 4-(2-furan-2-yl-ethyl)-((E)-2-nitro-vinyl)benzene (554 mg, 2.28 mmol) described in Manufacturing Example 80-1-5 and acetic acid (0.5 mL) was added sodium borohydride (129 mg, 3.42 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes at room temperature. Water was added dropwise into this reaction solution at room temperature while cooling appropriately. The reaction mixture was partitioned into water and ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride and dried over anhydrous magnesium

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sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (t-butylmethyl ether:heptane=5:95) to obtain the title compound (300 mg, 53percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 2.88-2.96 (4H, m), 3.29 (2H, t, J=7.2 Hz), 4.59 (2H, t, J=7.2 Hz), 5.95 (1H, m), 6.27 (1H, m), 7.10-7.16 (4H, m), 7.32 (1H, m) With sodium tetrahydroborate, acetic acid in tetrahydrofuran, dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys O E

O O

N O

O O

Rx-ID: 2195441 View in Reaxys 263/375 Yield

Conditions & References

80 %

With lithium aluminium tetrahydride, aluminium trichloride in tetrahydrofuran, Time= 16h, Ambient temperature McCarthy, James R.; McCowan, Jefferson; Zimmerman, Mark B.; Wenger, Marcia A.; Emmert, Lee W.; Journal of Medicinal Chemistry; vol. 29; nb. 9; (1986); p. 1586 - 1590 View in Reaxys HO

HO O

E N

Rx-ID: 2654913 View in Reaxys 264/375 Yield

Conditions & References

95 %

With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, T= 20 °C Zhang, Bang-Le; Wang, Fang-Dao; Yue, Jian-Min; Synlett; nb. 4; (2006); p. 567 - 570 View in Reaxys

86 %

With sodium tetrahydroborate in methanol, Time= 0.75h, Ambient temperature Dauzonne, Daniel; Royer, Rene; Synthesis; nb. 12; (1984); p. 1054 - 1057 View in Reaxys O N

O N

Rx-ID: 34059496 View in Reaxys 265/375 Yield

Conditions & References

63 %

O N

N Br

Rx-ID: 9687234 View in Reaxys 266/375 Yield

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol

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O N

Rx-ID: 35655297 View in Reaxys 267/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.33333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

O N

Rx-ID: 25770593 View in Reaxys 268/375 Yield

Conditions & References

44 %

79.1.3 :To an acetic acid (3.3 mL) and dimethyl sulfoxide (55 mL) solution of 1-cyclohexyloxy-4-((E)-2-nitro-vinyl)benzene (3.3 g, 13.1 mmol) described in Manufacturing Example 79-1-2 was added sodium borohydride (793 mg, 21 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1 hour at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1) to obtain the title compound (1.45 g, 44percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 1.26-1.43 (3H, m), 1.46-1.58 (3H, m), 1.79-1.81 (2H, m), 1.95-1.98 (2H, m), 3.23-3.27 (2H, m), 4.17-4.24 (1H, m), 4.55-4.58 (2H, m), 6.83-6.87 (2H, m), 7.08-7.10 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

Rx-ID: 25770603 View in Reaxys 269/375 Yield 65 %

Conditions & References 82.1.5 :To a mixed tetrahydrofuran-dimethyl sulfoxide (1:1, 10 mL) solution of 4-(2-(tetrahydrofuran-2-yl)-ethyl)((E)-2-nitro-vinyl)-benzene (646 mg, 2.61 mmol) described in Manufacturing Example 82-1-4 and acetic acid (0.6 mL) was added sodium borohydride (148 mg, 3.92 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes at room temperature. Water was added dropwise into the reaction mixture at room temperature while cooling appropriately. The reaction mixture was partitioned into water and ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH-silica gel column chromatography (ethyl acetate:heptane=2:8) to obtain the title compound (421 mg, 65percent). 1H-NMR Spectrum (CDCl ) δ (ppm): 1.40-1.55 (1H, m), 1.70-2.00 (5H, m), 2.60-2.80 (2H, m), 3.29 (2H, t, J=7.2 Hz), 3 3.70-3.90 (3H, m), 4.59 (2H, t, J=7.2 Hz), 7.11 (2H, d, J=8.4 Hz), 7.17 (2H, d, J=8.4 Hz) With sodium tetrahydroborate, acetic acid in tetrahydrofuran, dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

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Rx-ID: 35655263 View in Reaxys 270/375 Yield

Conditions & References

62%

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.333333h, T= 0 °C , Inert atmosphere Cai, Shunyou; Zhang, Shaolong; Zhao, Yaohong; Wang, David Zhigang; Organic Letters; vol. 15; nb. 11; (2013); p. 2660 - 2663 View in Reaxys

O HN

HN O

O N

Rx-ID: 17136714 View in Reaxys 271/375 Yield

Conditions & References Reaction Steps: 2 1: 43 percent / NaBH4 / ethanol / 1 h / 0 °C 2: 78 percent / 1 N aq. NaOH / 0.75 h / Ambient temperature With sodium hydroxide, sodium tetrahydroborate in ethanol Chand, Pooran; Babu, Yarlagadda S.; Bantia, Shanta; Chu, Naiming; Cole, L. Brent; Kotian, Pravin L.; Laver, W. Graeme; Montgomery, John A.; Pathak, Ved P.; Petty, Sandra L.; Shrout, David P.; Walsh, David A.; Walsh, Gerald M.; Journal of Medicinal Chemistry; vol. 40; nb. 25; (1997); p. 4030 - 4052 View in Reaxys

O O

Rx-ID: 2153939 View in Reaxys 272/375 Yield 83 %

Conditions & References With sodium tetrahydroborate, ion exchange resin in methanol, Ambient temperature Kabalka, George W.; Laila Guindi; Varma, Rajender S.; Tetrahedron; vol. 46; nb. 21; (1990); p. 7443 - 7457 View in Reaxys

83 %

75 %

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E E

Rx-ID: 8969902 View in Reaxys 273/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 3h, T= 25 °C Dhar; Bhattacharjya; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 40; nb. 11; (2001); p. 1140 - 1143 View in Reaxys

Rx-ID: 34059516 View in Reaxys 274/375 Yield

Conditions & References Reaction Steps: 3 1: sodium tetrahydroborate / methanol / 1.5 h / 20 °C / |Inert atmosphere 2: 10 Pd/C; hydrogen / methanol / |Inert atmosphere 3: ethanol / 18 h / 20 °C / |Inert atmosphere With sodium tetrahydroborate, 10 Pd/C, hydrogen in methanol, ethanol Anderson, James C.; Noble, Adam; Torres, Pascual Ribelles; Tetrahedron Letters; vol. 53; nb. 42; (2012); p. 5707 - 5710 View in Reaxys

O N

H 2N

H NH

H 2N

O N

Rx-ID: 24271273 View in Reaxys 275/375 Yield

Conditions & References

93%

227 : Isomer A: (+-) (cis) 5-[(4-methoxyphenyl)methyl]-3-methylpyrrolidin-2-imine, monohydrochloride EXAMPLES 227 Isomer A: (+-) (cis) 5-[(4-methoxyphenyl)methyl]-3-methylpyrrolidin-2-imine, monohydrochloride Isomer B: (+-) (trans) 5-[(4-methoxyphenyl)methyl]-3-methylpyrrolidin-2-imine, monohydrochloride STR232 227 A) 4Methoxy-b-nitrostyrene (25.0 g, 0.15 mole) was reacted with benzaldehyde (19.1 g, 0.18 mole) and 1,2-diaminobenzene (19.8 g, 0.18 mole) according to the procedure of Chikashita et. al. (Synth. Commun. 1985, 15 (6), 527) to yield methoxy-4-(2-nitroethyl)benzene (25.0 g, 93percent) as a yellow oil. With benzaldehyde Patent; G. D. Searle and Co.; US5883251; (1999); (A1) English View in Reaxys

O N

N O

N F

HN N

Rx-ID: 13489729 View in Reaxys 276/375 Yield

Conditions & References Reaction Steps: 2 1: NaBH4; SiO2 / propan-2-ol; CHCl3

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2: 42 percent / NaN3; NH4Cl / dimethylformamide With sodium tetrahydroborate, sodium azide, silica gel, ammonium chloride in chloroform, N,N-dimethyl-formamide, isopropyl alcohol Malancona, Savina; Colarusso, Stefania; Ontoria, Jesus M.; Marchetti, Antonella; Poma, Marco; Stansfield, Ian; Laufer, Ralph; Di Marco, Annalise; Taliani, Marina; Verdirame, Maria; Gonzalez-Paz, Odalys; Matassa, Victor G.; Narjes, Frank; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 17; (2004); p. 4575 - 4579 View in Reaxys

O O

O E

N O

Rx-ID: 2195878 View in Reaxys 277/375 Yield

Conditions & References

92 %

With sodium tetrahydroborate in methanol, ethyl acetate, Time= 0.25h, T= 0 °C Andrew, Robert G.; Raphael, Ralph A.; Tetrahedron; vol. 43; nb. 21; (1987); p. 4803 - 4816 View in Reaxys

90 %

With sodium tetrahydroborate, silica gel Maryanoff, Bruce E.; McComsey, David F.; Martin, Gregory E.; Shank, Richard P.; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 8; (1998); p. 983 - 988 View in Reaxys

O N

O O

N O

Rx-ID: 4050647 View in Reaxys 278/375 Yield

Conditions & References With sodium tetrahydroborate in methanol Baxter,I.; Swan,G.A.; Journal of the Chemical Society [Section] C: Organic; (1968); p. 468 - 470 View in Reaxys

N O

Rx-ID: 25770575 View in Reaxys 279/375 Yield 48 %

Conditions & References 68.1.3 :To an acetic acid (5.8 mL) and dimethyl sulfoxide (100 mL) solution of benzyl-(4-((E)-2-nitro-vinyl)-phenyl)amine (5.82 g, 22.9 mmol) described in Manufacturing Example 68-1-2 was added sodium borohydride (1.39 g, 36.6 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1 hour at room temperature. The mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-2:1) to obtain the title compound (2.79 g, 48percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.19-3.22 (2H, m), 4.32 (2H, s), 4.52-4.56 (3H, m), 6.60-6.62 (2H, m), 7.00-7.02 (2H, m), 7.27-7.37 (5H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

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Rx-ID: 25770584 View in Reaxys 280/375 Yield

Conditions & References 73.1.5 :To an acetic acid (1.5 mL) and dimethyl sulfoxide (26 mL) solution of (4-((E)-2-nitro-vinyl)-benzyl)-phenylamine (1.53 g, 6.02 mmol) described in Manufacturing Example 73-1-4 was added sodium borohydride (364 mg, 9.63 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1.5 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain the title compound (1.5 g). This compound was used in the subsequent reaction without being purified. 1HNMR Spectrum (CDCl3) δ (ppm): 3.29-3.33 (2H, m), 4.32 (2H, s), 4.59-4.62 (2H, m), 6.61-6.63 (2H, m), 6.70-6.74 (1H, m), 7.15-7.20 (4H, m), 7.33-7.35 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys O

E O

Rx-ID: 10404161 View in Reaxys 281/375 Yield

Conditions & References

90 %

With sodium tetrahydroborate Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.; Tetrahedron Letters; vol. 47; nb. 30; (2006); p. 5409 - 5413 View in Reaxys

O N

Rx-ID: 25756129 View in Reaxys 282/375 Yield 70 %

Conditions & References 1.1.2 :Manufacturing Example 1-1-2 1-Benzyloxy-4-(2-nitro-ethyl)-benzene; To a mixture of 1-benzyloxy-4-((E)-2-nitro-vinyl)-benzene (1.0 g, 3.9 mmol) described in Manufacturing Example 1-1-1, acetic acid (1 mL) and dimethyl sulfoxide (17 mL) was added sodium borohydride (250 mg, 6.3 mmol) at room temperature while cooling appropriately, and the reaction mixture was stirred for 40 minutes at room temperature. Water was added to the reaction mixture. The reaction mixture was partitioned into ethyl acetate and water. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (710 mg, 70percent).1H-NMR Spectrum (CDCl3) δ (ppm): 3.26 (2H, t, J=7.2 Hz), 4.56 (2H, t, J=7.2 Hz), 5.04 (2H, s), 6.92 (2H, d, J=8.4 Hz), 7.11 (2H, d, J=8.8 Hz), 7.30-7.42 (5H, m). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.666667h, T= 20 °C Stage 2: With water in dimethyl sulfoxide Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

70 %

1.1.2 :To a mixture of 1-benzyloxy-4-((E)-2-nitro-vinyl)-benzene (1.0 g, 3.9 mmol) described in Manufacturing Example 1-1-1, acetic acid (1 mL) and dimethyl sulfoxide (17 mL) was added sodium borohydride (250 mg, 6.3 mmol) at room temperature while cooling appropriately, and the reaction mixture was stirred for 40 minutes at room temperature. Water was added to the reaction mixture. The reaction mixture was partitioned into ethyl acetate and water. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column

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chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (710 mg, 70percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.26 (2H, t, J=7.2 Hz), 4.56 (2H, t, J=7.2 Hz), 5.04 (2H, s), 6.92 (2H, d, J=8.4 Hz), 7.11 (2H, d, J=8.8 Hz), 7.30-7.42 (5H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.666667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys 70 %

1.1.2 : 1-Benzyloxy-4-(2-nitro-ethyl)-benzene Manufacturing Example 1-1-2 1-Benzyloxy-4-(2-nitro-ethyl)-benzene To a mixture of 1-benzyloxy-4-((E)-2-nitro-vinyl)-benzene (1.0 g, 3.9 mmol) described in Manufacturing Example 1-1-1, acetic acid (1 mL), and dimethyl sulfoxide (17 mL) was added sodium borohydride (250 mg, 6.3 mmol) while suitable cooling, which was stirred for 40 minutes at room temperature. This reaction mixture was added with water and partitioned into ethyl acetate and water. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH-silica gel column chromatography (ethyl acetate:heptane=1:3), which gave the titled compound (710 mg, 70percent). 1H-NMR spectrum (CDCl ) δ (ppm): 3.26 (2H, t, J=7.2 Hz), 4.56 (2H, t, J=7.2 Hz), 5.04 (2H, s), 6.92 (2H, d, J=8.4 3 Hz), 7.11 (2H, d, J=8.8 Hz), 7.30-7.42 (5H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, T= 20 °C , Cooling Patent; MATSUKURA, Masayuki; US2010/331282; (2010); (A1) English View in Reaxys

O O

Rx-ID: 25769572 View in Reaxys 283/375 Yield

Conditions & References

57 %

61.1.3 :To an acetic acid (5.5 mL) and dimethyl sulfoxide (94 mL) solution of 1-benzyloxy-3-((E)-2-nitro-vinyl)-benzene (5.5 g, 21.5 mmol) described in Manufacturing Example 61-1-2 was added sodium borohydride (1.3 g, 34.4 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1.5 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1-4:1) to obtain the title compound (3.14 g, 57percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.17-3.21 (2H, m), 4.83-4.86 (2H, m), 5.07 (2H, s), 6.84-6.86 (1H, m), 6.88-6.90 (1H, m), 6.96-6.97 (1H, m), 7.20-7.24 (1H, m), 7.31-7.35 (1H, m), 7.37-7.41 (2H, m), 7.44-7.46 (2H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O O

Rx-ID: 29384976 View in Reaxys 284/375 Yield

Conditions & References With sodium tetrahydroborate in 1,4-dioxane, Time= 2h, Reflux

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Rx-ID: 30079526 View in Reaxys 285/375 Yield

Conditions & References To a mixture of LiBH4 (11.0 g, 500 mmol) and 300 ml. of THF was added TMSCI (108 g, 1 mol) at 0 0C. The reaction was stirred at 0 0C for 10 min, then added a solution of 1-bromo-2-ethyl-3-(2-nitrovinyl)benzene (25.5 g, 100 mmol) (Preparation 197) in 100 ml. of THF. The reaction mixture was warmed to room temperature and refluxed for 3 hours. After cooling to room temperature, 40 ml. of MeOH was added carefully. The solvent was concentrated, and diluted with 300 ml. of EtOAc and 100 ml. of water. The organic layer was dried over Na2SO4 and concentrated to give the crude product (19.0 g, 84.0percent yield). δH (CDCI3, 400 MHz): 8.30 (2H, brs), 7.33-7.36 (1 H, m), 7.04-7.19 (1 H, m), 6.85- 6.89(1 H, m), 3.09-3.19 (4H, m), 2.72-2.78 (2H, m), 1.08 (3H, t) ppm. MS (ES+): C10H14BrN requires 227; found 228 (M+H+). Stage 1: With lithium borohydride, chloro-trimethyl-silane in tetrahydrofuran, T= 0 - 20 °C , Reflux Stage 2: With methanol in tetrahydrofuran Patent; GLAXO GROUP LIMITED; BAILEY, James, Matthew; BIT, Rino, Antonio; DEMONT, Emmanuel, Hubert; HARRISON, Lee, Andrew; JONES, Katherine, Louise; SMETHURST, Christian, Alan, Paul; WITHERINGTON, Jason; WO2010/146105; (2010); (A1) English View in Reaxys

O N

O O

N O

Rx-ID: 25770502 View in Reaxys 286/375 Yield 77.1 %

Conditions & References 2.1.4 :Manufacturing Example 2-1-4 2-(4-(2-Nitro-ethyl)-benzyloxy)-pyridine; To a solution of 2-(4-((E)-2-nitro-vinyl)benzyloxy)-pyridine (21.0 g, 81.9 mmol) described in Manufacturing Example 2-1-3, acetic acid (21 mL) in dimethyl sulfoxide (200 mL) was added sodium borohydride (4.96 g, 131 mmol) at room temperature while cooling appropriately. After addition of sodium borohydride, the cooling bath was removed, followed by stirring for 15 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate. The ethyl acetate layer was washed with water twice and with saturated aqueous sodium chloride once, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (16.3 g, 77.1percent).1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.23 (2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.32(2H, s), 6.82-6.88 (1H, m), 6.96-7.01 (1H, m), 7.28 (2H, d, J=8.0 Hz), 7.38 (2H, d, J=8.0 Hz), 7.69-7.74 (1H, m), 8.15-8.19 (1H, m). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.25h, T= 20 °C Stage 2: With water in dimethyl sulfoxide, ethyl acetate, Product distribution / selectivity Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

77.1 %

1.1.4 :Manufacturing Example 1-1-42-(4-(2-Nitro-ethyl)-benzyloxy)-pyridine; To a solution of 2-(4-((E)-2-nitro-vinyl)benzyloxy)-pyridine (21.0 g, 81.9 mmol) described in Manufacturing Example 1-1-3, acetic acid (21 mL), and dimethyl sulfoxide (200 mL) was added sodium borohydride (4.96 g, 131 mmol) at room temperature while cooling suitably. After the addition of the sodium borohydride, the ice bath was removed, followed by stirring for 15 minutes at room temperature. The reaction solution was separated into water and ethyl acetate. The ethyl acetate layer was washed with water twice and with saline once, and this product was dried over anhydrous magnesium sulfate and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (16.3 g, 77.1percent).1H-NMR spectrum (DMSO-d6) δ (ppm): 3.23

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(2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.32 (2H, s), 6.82-6.88 (1H, m), 6.96-7.01 (1H, m), 7.28 (2H, d, J=8.0 Hz), 7.38 (2H, d, J=8.0 Hz), 7.69-7.74 (1H, m), 8.15-8.19 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, T= 20 °C , Cooling with ice, Product distribution / selectivity Patent; Eisai RandD Management Co. Ltd.; US2009/233883; (2009); (A1) English View in Reaxys 77.1 %

1.1.4 :Manufacturing Example 1-1-4 2-(4-(2-Nitro-ethyl)-benzyloxy)-pyridine To a solution of 2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (21.0 g, 81.9 mmol) described in Manufacturing Example 1-1-3, acetic acid (21 mL), and dimethyl sulfoxide (200 mL) was added sodium borohydride (4.96 g, 131 mmol) at room temperature and under suitable cooling. After the addition of sodium borohydride, the ice bath was removed and the reaction solution was stirred for 15 minutes at room temperature. The reaction solution was separated into water and ethyl acetate. The ethyl acetate layer was washed twice with water and once with saline, and was then dried over anhydrous magnesium sulfate and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the titled compound (16.3 g, 77.1percent). 1H-NMR spectrum (DMSO-d ) δ (ppm): 3.23 (2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.32 (2H, s), 6.82-6.88 (1H, 6 m), 6.96-7.01 (1H, m), 7.28 (2H, d, J=8.0 Hz), 7.38 (2H, d, J=8.0 Hz), 7.69-7.74 (1H, m), 8.15-8.19 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.25h, T= 20 °C , Cooling with ice, Product distribution / selectivity Patent; Tanaka, Keigo; US2010/105737; (2010); (A1) English View in Reaxys

77.1 %

2.1.4 :To a solution of 2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (21.0 g, 81.9 mmol) described in Manufacturing Example 2-1-3, acetic acid (21 mL) in dimethyl sulfoxide (200 mL) was added sodium borohydride (4.96 g, 131 mmol) at room temperature while cooling appropriately. After addition of sodium borohydride, the cooling bath was removed, followed by stirring for 15 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate. The ethyl acetate layer was washed with water twice and with saturated aqueous sodium chloride once, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (16.3 g, 77.1percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.23 (2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.32 (2H, s), 6.82-6.88 (1H, m), 6.96-7.01 (1H, m), 7.28 (2H, d, J=8.0 Hz), 7.38 (2H, d, J=8.0 Hz), 7.69-7.74 (1H, m), 8.15-8.19 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.25h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys 2.2.4 :Manufacturing Example 2-2-4 2-(4-(2-Nitro-ethyl)-benzyloxy)-pyridine; To a dimethylsulfoxide (150 mL) solution of acetic acid (7.4 mL) and 2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (30.8 g, 120 mmol) described in Manufacturing Example 2-2-3 was added sodium borohydride (2.45 g, 64.8 mmol) at 30° C. or less. The reaction solution was stirred at room temperature for 40 minutes. To the reaction solution were added water, ethyl acetate and diethyl ether at 30° C. or less to partition it into water and an organic layer. The water layer was extracted with ethyl acetate. This ethyl acetate layer was combined with the organic layer obtained previously, washed with water (3 times) and aqueous sodium chloride (1 time), dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:4) to obtain the title compound (15.2 g). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.666667h, T= 20 - 30 °C Stage 2: With water in diethyl ether, dimethyl sulfoxide, ethyl acetate, T= 30 °C , Product distribution / selectivity Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys 1.3.4 : 2-(4-(2-Nitro-ethyl)-benzyloxy)-pyridine

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To a solution of 2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine described in Preparation Example 1-3-3 (21.0 g, 81.9 mmol), acetic acid (21 mL) and dimethylsulfoxide (200 mL) was added sodium borohydride (4.96 g, 131 mmol), while being suitably cooled at room temperature. After sodium borohydride was added, the cold bath was removed, the solution was stirred at room temperature for 15 minutes. The reaction solution was partitioned into water and ethyl acetate. The ethyl acetate layer was washed twice with water and once with sodium chloride water, this was dried over anhydrous magnesium sulfate, and the solvent thereof was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:3) to obtain the title compound (16.3 g). 1H-NMR Spectrum (DMSO-d ) δ (ppm): 3.23 (2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.32 (2H, s), 6.82-6.88 (1H, 6 m), 6.96-7.01 (1H, m), 7.28 (2H, d, J=8.0 Hz), 7.38 (2H, d, J=8.0 Hz), 7.69-7.74 (1H, m), 8.15-8.19 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.25h, T= 20 °C Patent; Niijima, Jun; Nakamoto, Kazutaka; Matsukura, Masayuki; Tanaka, Keigo; Yamamoto, Eiichi; Minamisono, Takuma; US2008/275244; (2008); (A1) English View in Reaxys 1.4.4 : 2-(4-(2-Nitro-ethyl)-benzyloxy)-pyridine To a solution of 2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine described in Preparation Example 1-4-3 (30.8 g, 120 mmol) and acetic acid (7.4 mL) in dimethylsulfoxide (150 mL) was added sodium borohydride (2.45 g, 64.8 mmol) at below 30° C. The reaction solution was stirred at room temperature for 40 minutes. To the reaction solution were added water and ethyl acetate and diethyl ether at below 30° C., and partitioned into water and organic layer. The aqueous layer was extracted with ethyl acetate. The organic layer and ethyl acetate layer were combined, washed with water (3 times) and sodium chloride water (once), dried over anhydrous magnesium sulfate and then filtered. The filtrate thereof was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:4) to obtain the title compound (15.2 g). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.666667h, T= 20 - 30 °C , Product distribution / selectivity Patent; Niijima, Jun; Nakamoto, Kazutaka; Matsukura, Masayuki; Tanaka, Keigo; Yamamoto, Eiichi; Minamisono, Takuma; US2008/275244; (2008); (A1) English View in Reaxys

O N

O O

Rx-ID: 25770563 View in Reaxys 287/375 Yield 64 %

Conditions & References 60.1.3 :To an acetic acid (2.5 mL) and dimethyl sulfoxide (43 mL) solution of 2-(3-((E)-2-nitro-vinyl)-phenoxymethyl)pyridine (2.56 g, 10 mmol) described in Manufacturing Example 60-1-2 was added sodium borohydride (605 mg, 16 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1.5 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1-4:1-1:1) to obtain the title compound (1.66 g, 64percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.20-3.23 (2H, m), 4.83-4.87 (2H, m), 5.44 (2H, s), 6.86-6.89 (1H, m), 6.91-6.93 (1H, m), 7.00 (1H, m), 7.26-7.30 (1H, m), 7.64-7.67 (1H, m), 7.86-7.88 (1H, m), 8.21-8.24 (1H, m), 8.75-8.76 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

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O O

N N

Rx-ID: 34059537 View in Reaxys 288/375 Yield

O O

O N O

O F

Rx-ID: 25775032 View in Reaxys 289/375 Yield

Conditions & References 81.1.1 :To an N,N-dimethylformamide (30.0 mL) solution of 3-fluorophenol (5.43 g, 48.4 mmol) and 4-fluorobenzaldehyde (3.00 g, 24.2 mmol) was added potassium carbonate (10.1 g, 72.5 mmol) under nitrogen atmosphere, which was stirred for 16 hours at 80° C. The reaction mixture was cooled to room temperature and water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:15-->1:10) to obtain a mixture with the starting material (6.00 g). To an acetic acid (50.0 mL) solution of this mixture (6.0 g) were added nitromethane (6.78 g, 111 mmol) and ammonium acetate (3.42 g, 44.4 mmol) at room temperature, which was stirred for 4 hours at 110° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain a crude product (5.5 g). To a dimethyl sulfoxide (40.0 mL) solution of this crude product (5.5 g) and acetic acid (5.00 mL) was added sodium borohydride (1.28 g, 33.9 mmol) at room temperature while cooling appropriately, which was stirred for 5 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (2.10 g, 37.9percent). 1H-NMR Spectrum (DMSO-d ) δ (ppm): 3.24 (2H, t, J=6.8 Hz), 4.86 (2H, t, J=6.8 Hz), 6.78-6.85 (2H, m), 6.94-6.98 6 (1H, m), 7.03 (2H, d, J=8.0 Hz), 7.33 (2H, d, J=8.0 Hz), 7.40-7.42 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.0833333h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

N F

N O

Rx-ID: 25775033 View in Reaxys 290/375 Yield

Conditions & References 83.1.2 :To an acetic acid (30.0 mL) solution of 4-(2-fluoro-phenoxy)-benzaldehyde (3.00 g, 13.9 mmol) described in Manufacturing Example 83-1-1 were added nitromethane (4.24 g, 69.5 mmol) and ammonium acetate (2.14 g, 27.8 mmol) under nitrogen atmosphere, which was stirred for 3 hours at 110° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was

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concentrated under a reduced pressure to obtain a crude product (3.60 g). To a dimethyl sulfoxide (50.0 mL) solution of this crude product (3.60 g) and acetic acid (3.00 mL) was added sodium borohydride (789 mg, 20.9 mmol) at room temperature while cooling appropriately, which was stirred for 20 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:10-->1:5) to obtain the title compound (1.80 g, 49.6percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.20 (2H, d, J=7.2 Hz), 4.83 (2H, d, J=7.2 Hz), 6.91-6.93 (2H, m), 7.13-7.17 (1H, m), 7.20-7.29 (4H, m), 7.36-7.41 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.333333h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

Rx-ID: 38199470 View in Reaxys 291/375 Yield

Conditions & References

80 %

1,4-Dimethoxy-2-(2-nitroethyl)naphthalene (12) To a solution of NaBH4 (0.5g, 0.014mol) in ethyl acetate-ethanol (20ml, 8:2), 1,4-dimethoxy-2-((E)-2-nitrovinyl) naphthalene (16, 2g, 0.007mol) was added portion wise at 15-20°C. The contents were stirred at room temperature for 1h and the reaction was monitored by TLC. Usual work up followed by column chromatographic purification over silica gel provided, 1,4-dimethoxy-2-(2-nitroethyl)naphthalene (13). Yield: 1.6g, (80percent) With sodium tetrahydroborate in ethanol, ethyl acetate, T= 15 - 20 °C Limaye, Rohan A.; Natu, Arun D.; Paradkar, Madhusudan V.; Synthetic Communications; vol. 44; nb. 17; (2014); p. 2503 - 2509 View in Reaxys

O N

Rx-ID: 25770590 View in Reaxys 292/375 Yield

Conditions & References

47 %

77.1.3 :To an acetic acid (4.1 mL) and dimethyl sulfoxide (70 mL) solution of 3-(4-((E)-2-nitro-vinyl)-phenoxymethyl)thiophene (4.1 g, 15.7 mmol) described in Manufacturing Example 77-1-2 was added sodium borohydride (950 mg, 25.1 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1.5 hours at room temperature. The mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-2:1) to obtain the title compound (1.93 g, 47percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.24-3.28 (2H, m), 4.55-4.59 (2H, m), 5.05 (2H, s), 6.91-6.93 (2H, m), 7.11-7.15 (3H, m), 7.31-7.32 (1H, m), 7.34-7.36 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1.5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

F N O

F O

O N

F N

Rx-ID: 40573304 View in Reaxys 293/375

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Yield

Rx-ID: 25775026 View in Reaxys 294/375 Yield

Conditions & References 62.1.5 :To a mixture of 4-(5-chloro-furan-2-ylmethyl)-benzaldehyde (270 mg, 1.2 mmol) described in Manufacturing Example 62-1-4 and acetic acid (3 mL) were added nitromethane (500 μL, 9.3 mmol) and ammonium acetate (290 mg, 3.7 mmol) at room temperature, which was stirred for 3 hours at 100° C. The reaction mixture was cooled to room temperature, and extracted by addition of water and ethyl acetate. This organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and was concentrated under a reduced pressure. To a mixture of acetic acid (0.6 mL) and dimethyl sulfoxide (10 mL) was added sodium borohydride (76 mg, 2.0 mmol) at room temperature while cooling appropriately, which was stirred for 10 minutes at room temperature. Water was added to the reaction solution at room temperature, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride. The organic layer was concentrated under a reduced pressure, and the residue was purified by neutral silica gel column chromatography (ethyl acetate:heptane=1:5) to obtain the title compound (210 mg, 62percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.30 (2H, t, J=7.4 Hz), 3.89 (2H, s), 4.60 (2H, t, J=7.4 Hz), 5.97 (1H, d, J=3.1 Hz), 6.04 (1H, d, J=3.1 Hz), 7.15 (2H, d, J=8.2 Hz), 7.19 (2H, d, J=8.2 Hz). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O HN

HN O

N O

Rx-ID: 4796845 View in Reaxys 295/375 Yield

Conditions & References

43 %

With sodium tetrahydroborate in ethanol, Time= 1h, T= 0 °C Chand, Pooran; Babu, Yarlagadda S.; Bantia, Shanta; Chu, Naiming; Cole, L. Brent; Kotian, Pravin L.; Laver, W. Graeme; Montgomery, John A.; Pathak, Ved P.; Petty, Sandra L.; Shrout, David P.; Walsh, David A.; Walsh, Gerald M.; Journal of Medicinal Chemistry; vol. 40; nb. 25; (1997); p. 4030 - 4052 View in Reaxys

O O

N O

HN O

Rx-ID: 16786501 View in Reaxys 296/375 Yield

Conditions & References Reaction Steps: 3 1: 90 percent / NaBH4, silica gel 2: cyclohexene / 10percent Pd/C / ethanol / Heating With sodium tetrahydroborate, silica gel, cyclohexene, palladium on activated charcoal in ethanol

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Maryanoff, Bruce E.; McComsey, David F.; Martin, Gregory E.; Shank, Richard P.; Bioorganic and Medicinal Chemistry Letters; vol. 8; nb. 8; (1998); p. 983 - 988 View in Reaxys

Rx-ID: 34059528 View in Reaxys 297/375 Yield

Rx-ID: 34059533 View in Reaxys 298/375 Yield

O O

N O

Rx-ID: 20260275 View in Reaxys 299/375 Yield

Conditions & References Reaction Steps: 2 1: 73 percent / NaBH4 / tetrahydrofuran; methanol 2: 96 percent / pyridinium p-toluenesulfonate / CH2Cl2 / Ambient temperature With sodium tetrahydroborate, pyridinium p-toluenesulfonate in tetrahydrofuran, methanol, dichloromethane Tius; Kerr; Journal of the American Chemical Society; vol. 114; nb. 15; (1992); p. 5959 - 5966 View in Reaxys

O N O

O N

Rx-ID: 2843918 View in Reaxys 300/375

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Yield

Conditions & References

100 %

With sodium tetrahydroborate in tetrahydrofuran, isopropyl alcohol, Time= 24h, Ambient temperature Barton, Derek H. R.; Motherwell, William B.; Simon, Ethan S.; Zard, Samir Z.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1986); p. 2243 - 2252 View in Reaxys

N O

O O

Rx-ID: 25770505 View in Reaxys 301/375 Yield

Conditions & References

56 %

3.1.4 :Manufacturing Example 3-1-4 2-Methyl-6-(4-(2-nitro-ethyl)-benzyloxy)pyridine; To a solution of 2-methyl-6-(4((E)-2-nitro-vinyl)-benzyloxy)-pyridine (5.00 g, 18.5 mmol) described in Manufacturing Example 3-1-3 and acetic acid (5 mL) in dimethyl sulfoxide (50 mL) was added sodium borohydride (1.2 g, 29.6 mmol) under nitrogen atmosphere at room temperature while cooling appropriately, which was stirred for 10 minutes at room temperature. Water was then added dropwise. The mixture was partitioned into water and ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5 then 1:2) to obtain the title compound (2.8 g, 56percent).1H-NMR Spectrum (DMSO-d6) δ (ppm): 2.39 (3H, s), 3.22 (2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.28 (2H, s), 6.64 (1H, d, J=8.0 Hz), 7.84 (1H, d, J=8.0 Hz), 7.28 (2H, d, J=7.6 Hz), 7.39 (2H, d, J=7.6 Hz), 7.59 (1H, t, J=8.0 Hz). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Stage 2: With water in dimethyl sulfoxide Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

56 %

3.1.4 :To a solution of 2-methyl-6-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (5.00 g, 18.5 mmol) described in Manufacturing Example 3-1-3 and acetic acid (5 mL) in dimethyl sulfoxide (50 mL) was added sodium borohydride (1.2 g, 29.6 mmol) under nitrogen atmosphere at room temperature while cooling appropriately, which was stirred for 10 minutes at room temperature. Water was then added dropwise. The mixture was partitioned into water and ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5 then 1:2) to obtain the title compound (2.8 g, 56percent). 1H-NMR Spectrum (DMSO-d ) δ (ppm): 2.39 (3H, s), 3.22 (2H, t, J=6.8 Hz), 4.85 (2H, t, J=6.8 Hz), 5.28 (2H, s), 6.64 6 (1H, d, J=8.0 Hz), 7.84 (1H, d, J=8.0 Hz), 7.28 (2H, d, J=7.6 Hz), 7.39 (2H, d, J=7.6 Hz), 7.59 (1H, t, J=8.0 Hz). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

O O

Rx-ID: 25770541 View in Reaxys 302/375 Yield 35.1 %

Conditions & References 43.1.4 :Manufacturing Example 43-1-4 4-Methyl-2-(4(2-nitro-ethyl)-benzyloxy)pyridine; To a dimethyl sulfoxide (50 mL) solution of 4-methyl-2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (3.10 g, 11.5 mmol) described in Manufacturing Example 43-1-3 and acetic acid (3.10 mL) was added sodium borohydride (733 mg, 18.4 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes. Water was then added dropwise into the reaction solution at room temperature while cooling appropriately, and the reaction mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5-->1:2) to obtain the title compound (1.10 g, 35.1percent).1H-NMR Spectrum (DMSO-d6) δ (ppm): 2.27 (3H, s), 3.22 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 5.29 (2H, s), 6.69 (1H, s), 6.82 (1H, d, J=5.2 Hz), 7.27 (2H, d, J=8.0 Hz), 7.37 (2H, d, J=8.0 Hz), 8.02 (1H, d, J=5.2 Hz).

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Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Stage 2: With water in dimethyl sulfoxide, T= 20 °C Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys 35.1 %

43.1.4 :To a dimethyl sulfoxide (50 mL) solution of 4-methyl-2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (3.10 g, 11.5 mmol) described in Manufacturing Example 43-1-3 and acetic acid (3.10 mL) was added sodium borohydride (733 mg, 18.4 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes. Water was then added dropwise into the reaction solution at room temperature while cooling appropriately, and the reaction mixture was extracted with ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5-->1:2) to obtain the title compound (1.10 g, 35.1percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 2.27 (3H, s), 3.22 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 5.29 (2H, s), 6.69 (1H, s), 6.82 (1H, d, J=5.2 Hz), 7.27 (2H, d, J=8.0 Hz), 7.37 (2H, d, J=8.0 Hz), 8.02 (1H, d, J=5.2 Hz). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N

O O

Rx-ID: 25770543 View in Reaxys 303/375 Yield 54.3 %

Conditions & References 44.1.4 :Manufacturing Example 44-1-4 5-Methyl-2-(4-(2-nitro-ethyl)-benzyloxy)pyridine; To a dimethyl sulfoxide (40.0 mL) solution of 5-methyl-2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (3.50 g, 12.9 mmol) described in Manufacturing Example 44-1-3 and acetic acid (3.50 mL) was added sodium borohydride (822 mg, 20.6 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:4) to obtain the title compound (1.91 g, 54.3percent). 1H-NMR Spectrum (DMSO-d ) δ (ppm): 2.20 (3H, s), 3.22 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 5.27 (2H, s), 6 6.76-6.78 (1H, m), 7.27 (2H, d, J=8.0 Hz), 7.36 (2H, d, J=8.0 Hz), 7.52-7.55 (1H, m), 7.97-7.98 (1H, m). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Stage 2: With water in dimethyl sulfoxide, T= 20 °C Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

54.3 %

44.1.4 :To a dimethyl sulfoxide (40.0 mL) solution of 5-methyl-2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (3.50 g, 12.9 mmol) described in Manufacturing Example 44-1-3 and acetic acid (3.50 mL) was added sodium borohydride (822 mg, 20.6 mmol) at room temperature while cooling appropriately under nitrogen atmosphere, which was stirred for 10 minutes. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:4) to obtain the title compound (1.91 g, 54.3percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 2.20 (3H, s), 3.22 (2H, t, J=6.8 Hz), 4.84 (2H, t, J=6.8 Hz), 5.27 (2H, s), 6.76-6.78 (1H, m), 7.27 (2H, d, J=8.0 Hz), 7.36 (2H, d, J=8.0 Hz), 7.52-7.55 (1H, m), 7.97-7.98 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 0.166667h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

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F O

N O

O F

Rx-ID: 9690706 View in Reaxys 304/375 Yield

O O

Rx-ID: 25915506 View in Reaxys 305/375 Yield

Conditions & References

43.3 %

354 :1-benzyloxy-3-fluoro-5-(2-nitro-ethyl)-benzene Add sodium borohydride (1.69 g, 44.64 mmol) to 1-benzyloxy-3-fluoro-5-((E)-2-nitro-vinyl)-benzene (3.05 g, 11.16 mmol) and silica gel (22 g) in chloroform (112 mL) and isopropanol (33 mL) at room temperature in portions over 5 minutes. Stir at room temperature 90 minutes and filter. Concentrate and dissolve in ethyl acetate. Wash (10percent potassium carbonate and saturated aqueous sodium chloride), dry over magnesium sulfate, filter and concentrate. Purify on 120 g silica gel eluding with 100:0 to 80:20 hexanes:ethyl acetate to afford 1.33 g (43.3percent) of the desired compound as an oil. 1H-NMR (400 MHz, CDCl ) δ 7.42-7.32 (m, 5H), 6.62-6.58 (m, 2H), 6.53 (dt, 1H, J=5.3, 3.1 Hz), 5.03 (s, 2H), 4.59 (t, 3 2H, J=7.3 Hz), 3.27 (t, 2H, J=7.3 Hz). With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 1.58333h, T= 20 °C Patent; Broughton, Howard Barff; Dally, Robert Dean; Durham, Timothy Barrett; Gonzalez-Garcia, Maria Rosario; Sa, Lilly; Hahn, Patric James; Henry, Kenneth James; Kohn, Todd Jonathan; McCarthy, James Ray; Shepherd, Timothy Alan; Erickson, Jon Andre; Bueno Melendo, Ana Belen; US2007/225267; (2007); (A1) English View in Reaxys

F O N

O O

N O

Rx-ID: 25770561 View in Reaxys 306/375 Yield 55 %

Conditions & References 59.1.4 :To an acetic acid (1.7 mL) and dimethyl sulfoxide (29 mL) solution of 4-fluoro-2-(4-((E)-2-nitro-vinyl)-benzyloxy)-pyridine (1.72 g, 6.27 mmol) described in Manufacturing Example 59-1-3 was added sodium borohydride (380 mg, 10 mmol) at room temperature while cooling appropriately. This mixture was stirred for 5 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-1:1) to obtain the title compound (960 mg, 55percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.33-3.37 (2H, m), 4.61-4.65 (2H, m), 5.09 (2H, s), 6.81-6.83 (1H, m), 6.91-6.92 (1H, m), 7.25-7.27 (3H, m), 7.36-7.38 (1H, m), 8.20-8.22 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 5h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English

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View in Reaxys F O

N N

O O

N O

Rx-ID: 25775023 View in Reaxys 307/375 Yield

Conditions & References

46 %

55.1.4 :Manufacturing Example 55-1-4 2-Fluoro-6-(4-(2-nitro-ethyl)-benzyloxy)-pyridine; To a dimethyl sulfoxide (58.5 mL) solution of 2-fluoro-6-(4-(E)-2-nitro-vinyl)-benzyloxy)-pyridine (3.44 g, 12.5 mmol) described in Manufacturing Example 55-1-3 and acetic acid (3.44 mL) was added sodium borohydride (757 mg, 20 mmol) at room temperature while cooling appropriately. This mixture was stirred for 4 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1-4:1) to obtain the title compound (1.6 g, 46percent).1H-NMR Spectrum (CDCl3) δ (ppm): 3.31-3.35 (2H, m), 4.60-4.63 (2H, m), 5.31 (2H, s), 6.48-6.50 (1H, m), 6.64-6.67 (1H, m), 7.22-7.24 (2H, m), 7.41-7.43 (2H, m), 7.63-7.69 (1H, m). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 4h, T= 20 °C Stage 2: With water in dimethyl sulfoxide, ethyl acetate Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

46 %

55.1.4 :To a dimethyl sulfoxide (58.5 mL) solution of 2-fluoro-6-(4-(E)-2-nitro-vinyl)-benzyloxy)-pyridine (3.44 g, 12.5 mmol) described in Manufacturing Example 55-1-3 and acetic acid (3.44 mL) was added sodium borohydride (757 mg, 20 mmol) at room temperature while cooling appropriately. This mixture was stirred for 4 hours at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with saturated aquesous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=10:1-4:1) to obtain the title compound (1.6 g, 46percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 3.31-3.35 (2H, m), 4.60-4.63 (2H, m), 5.31 (2H, s), 6.48-6.50 (1H, m), 6.64-6.67 (1H, m), 7.22-7.24 (2H, m), 7.41-7.43 (2H, m), 7.63-7.69 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 4h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys

O N O

F N

Rx-ID: 25775024 View in Reaxys 308/375 Yield 56 %

Conditions & References 56.1.4 :Manufacturing Example 56-1-4 (5-Fluoro-2-(4-(2-nitro-ethyl)-benzyloxy)-pyridine; To a dimethyl sulfoxide (49 mL) solution of 5-fluoro-2-(4-((E)-nitro-vinyl)-benzyloxy)-pyridine (2.9 g, 10.6 mmol) described in Manufacturing Example 56-1-3 and acetic acid (2.9 mL) was added sodium borohydride (642 mg, 17 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1 hour at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH-silica gel column chromatography (heptane:ethyl acetate=10:1) to obtain the title compound (1.63 g, 56percent).1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.21-3.25 (2H, m), 4.83-4.87 (2H, m), 5.15 (2H, s), 7.31 (2H, d, J=8 Hz), 7.40 (2H, d, J=8 Hz), 7.44-7.48 (1H, m), 7.54-7.57 (1H, m), 8.18-8.19 (1H, m). Stage 1: With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h, T= 20 °C Stage 2: With water in dimethyl sulfoxide, ethyl acetate Patent; Tanaka, Keigo; Yamamoto, Eiichi; Watanabe, Naoaki; US2009/82403; (2009); (A1) English View in Reaxys

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56 %

56.1.4 :To a dimethyl sulfoxide (49 mL) solution of 5-fluoro-2-(4-((E)-nitro-vinyl)-benzyloxy)-pyridine (2.9 g, 10.6 mmol) described in Manufacturing Example 56-1-3 and acetic acid (2.9 mL) was added sodium borohydride (642 mg, 17 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1 hour at room temperature. This mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH-silica gel column chromatography (heptane:ethyl acetate=10:1) to obtain the title compound (1.63 g, 56percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 3.21-3.25 (2H, m), 4.83-4.87 (2H, m), 5.15 (2H, s), 7.31 (2H, d, J=8 Hz), 7.40 (2H, d, J=8 Hz), 7.44-7.48 (1H, m), 7.54-7.57 (1H, m), 8.18-8.19 (1H, m). With sodium tetrahydroborate, acetic acid in dimethyl sulfoxide, Time= 1h, T= 20 °C Patent; Eisai RandD Management Co., Ltd.; US2007/105904; (2007); (A1) English View in Reaxys O

Rx-ID: 10701486 View in Reaxys 309/375 Yield

Conditions & References

86 %

P14.d :d) Preparation of 4-bromo-2-chloro-1-(2-nitro-propyl)-benzene <n="46"/>A solution of 4-bromo-2-chloro-1((E)-2-nitro-propenyl)-benzene (6.1 g, 22.1 mmol) in 40 ml methanol was cooled to 00C under a nitrogen atmosphere. Sodium borohydride (2.52 g, 66.3 mmol) was added slowly. The reaction mixture was stirred at ambient temperature for 6 h and ethyl acetate was added. After removal of the solvent the residue was dissolved in water and extracted with ethyl acetate. The organic phase was washed with water and brine and dried over sodium sulphate. The solvent was evaporated and 5.5 g (89percent of theory) of 4- bromo-2-chloro-1-(2-nitro-propyl)-benzene were obtained (purity: 86percent). 1HNMR (400 MHz, CDCI3): 1.5 δ (d, 3H ), 3.15 δ (dd,1 H1CHH), 3.35 δ (dd,1 H1CHH), 4.85 δ (m, CHN), 7.05 δ (d, 1 H), 7.3 δ (dd, 1 H), 7.5 δ (d, 1 H) MS [M+H]+ (C9H9BrCINO2) (248/249/250) Stage 1: With sodium tetrahydroborate in methanol, Time= 6h, T= 0 - 20 °C Stage 2: With water Patent; SYNGENTA PARTICIPATIONS AG; SYNGENTA LIMITED; WO2007/141009; (2007); (A1) English View in Reaxys O

O O

N N O

Rx-ID: 34059529 View in Reaxys 310/375 Yield

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O O

Rx-ID: 34059531 View in Reaxys 311/375 Yield

O O

N F

O O

Rx-ID: 9690855 View in Reaxys 312/375 Yield

Rx-ID: 2079667 View in Reaxys 313/375 Yield 93 %

Conditions & References With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 - 5 °C Ranu, Brindaban C.; Chakraborty, Rupak; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3579 - 3582 View in Reaxys

93 %

With zinc(II) tetrahydroborate in DME, Time= 6h, T= 0 °C Ranu; Chakraborty; Tetrahedron; vol. 48; nb. 25; (1992); p. 5317 - 5322 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, Time= 2h, Reflux Wang, Yan-Xiang; Wang, Yu-Ping; Zhang, Hao; Kong, Wei-Jia; Li, Ying-Hong; Liu, Fei; Gao, Rong-Mei; Liu, Ting; Jiang, Jian-Dong; Song, Dan-Qing; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 21; (2009); p. 6004 - 6008 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, N,N-dimethyl-formamide, T= 0 °C Leese, Mathew P.; Jourdan, Fabrice; Dohle, Wolfgang; Kimberley, Meriel R.; Thomas, Mark P.; Bai, Ruoli; Hamel, Ernest; Ferrandis, Eric; Potter, Barry V. L.; ACS Medicinal Chemistry Letters; vol. 3; nb. 1; (2012); p. 5 - 9 View in Reaxys

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O E N

Rx-ID: 2079669 View in Reaxys 314/375 Yield

Conditions & References

95 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys

80 %

50 %

With sodium tetrahydroborate in 1,4-dioxane, N,N-dimethyl-formamide, Time= 6h, T= 0 - 20 °C Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Dohle, Wolfgang; Hamel, Ernest; Ferrandis, Eric; Fiore, Ann; Kasprzyk, Philip G.; Potter, Barry V. L.; ChemMedChem; vol. 9; nb. 1; (2014); p. 85 - 108 View in Reaxys

O O

N O

Rx-ID: 2200668 View in Reaxys 315/375 Yield

Conditions & References

95 %

With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 0.75h, T= 30 °C Bhattacharjya, Anup; Mukhopadhyay, Ranjan; Pakrashi, Satyesh C.; Synthesis; nb. 9; (1985); p. 886 - 887 View in Reaxys

N O

Rx-ID: 29384978 View in Reaxys 316/375 Yield 65 %

Conditions & References With lithium aluminium tetrahydride in tetrahydrofuran, diethyl ether, Time= 3h, T= 0 - 60 °C Li, Xiaomin; Chen, Zhengping; Tang, Jie; Liu, Chunyi; Zou, Pei; Huang, Hongbo; Tan, Cheng; Yu, Huixin; Archiv der Pharmazie; vol. 347; nb. 5; (2014); p. 313 - 319 View in Reaxys With sodium tetrahydroborate in 1,4-dioxane, Time= 2h, Reflux Wang, Yan-Xiang; Wang, Yu-Ping; Zhang, Hao; Kong, Wei-Jia; Li, Ying-Hong; Liu, Fei; Gao, Rong-Mei; Liu, Ting; Jiang, Jian-Dong; Song, Dan-Qing; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 21; (2009); p. 6004 - 6008 View in Reaxys With potassium borohydride in tetrahydrofuran Li, Wei; Zhang, Li; Xu, Lili; Yuan, Congmin; Du, Peng; Chen, Jiaojiao; Zhen, Xuechu; Fu, Wei; Chemical Biology and Drug Design; (2016); p. 599 - 607 View in Reaxys

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O O

Rx-ID: 43233147 View in Reaxys 317/375 Yield

Conditions & References With potassium borohydride Li, Wei; Zhang, Li; Xu, Lili; Yuan, Congmin; Du, Peng; Chen, Jiaojiao; Zhen, Xuechu; Fu, Wei; Chemical Biology and Drug Design; (2016); p. 599 - 607 View in Reaxys

O O

O Cl

Rx-ID: 34059530 View in Reaxys 318/375 Yield

O O

N Cl

Rx-ID: 34059535 View in Reaxys 319/375 Yield

O O

Rx-ID: 9690838 View in Reaxys 320/375 Yield

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol

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O N

Rx-ID: 11053351 View in Reaxys 321/375 Yield

Conditions & References

80 %

With tris(pentafluorophenyl)borate in dichloromethane, Time= 12h, T= 20 °C Chandrasekhar, Srivari; Chandrashekar, Gudise; Reddy, Marepally Srinivasa; Srihari, Pabbaraja; Organic and Biomolecular Chemistry; vol. 4; nb. 9; (2006); p. 1650 - 1652 View in Reaxys

O Br

Rx-ID: 29878027 View in Reaxys 322/375 Yield 91 %

Conditions & References Preparation of 1-bromo-2,3-dimethoxy-4-(2-nitroethyl)benzene To a stirred suspension of NaBH4 (5 equiv.) in 10 mL 1,4-dioxane/EtOH (2:1) was added a solution of 1-bromo-2,3dimethoxy-4-(2-nitrovinyl)benzene (1 mmol) in 1,4-dioxane (5 mL) drop-wise at 0 °C. After this addition, the reaction mixture was stirred for one and half hour. The resulting mixture was diluted with ice-water and quenched with 50percent aq AcOH. The resulting suspension was concentrated and then partitioned between NaHCO3 and CH2Cl2. Column using 10percent EtOAc in hexane. (Yield: 74 mg product from 86 mg starting material). 1H NMR (400 MHz) (CDCl3) δ 7.25 (d, J = 8.0 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 4.62 (t, J = 8.0 Hz, 2H), 3.95 (s, 3H), 3.89 (s, 3H), 3.29 (t, J = 4.0 Hz, 2H). With sodium tetrahydroborate in 1,4-dioxane, ethanol, Time= 1.5h, T= 0 °C Parhi, Ajit; Lu, Songfeng; Kelley, Cody; Lavoie, Edmond J.; Kaul, Malvika; Pilch, Daniel S.; Bioorganic and Medicinal Chemistry Letters; vol. 22; nb. 22; (2012); p. 6962 - 6966,5 View in Reaxys 17.d :To a stirred suspension OfNaBH4(S equiv.) in 10 mL 1 ,4-dioxane/EtOH (2:1) was added a solution of l-bromo-2,3-dimethoxy-4-(2-nitrovinyl)benzene (1 mmol) in 1,4-dioxane (5 mL) dropwise at 0 0C. After this addition, the reaction mixture was stirred for one and half hour. The resulting mixture was diluted with ice- water and quenched with 50percent aq AcOH. The resulting suspension was concentrated and then partitioned between NaHCO3 and CH2Cl2. Column using 10percent EtOAc in hexane. (Yield: 74 mg product from 86 mg starting material). 1H NMR (400 MHz) (CDCl3) δ 3.29 (t, J = 4.0Hz, 2H), 3.89 (s, 3H), 3.95 (s, 3H), 4.62 (t, J = 8.0 Hz, 2H), 6.83 (d, J = 8.0 Hz, IH), 7.25 (d, J = 8.0 Hz, IH). e. Preparation of Compound With sodium tetrahydroborate, ethanol in 1,4-dioxane, Time= 1.5h, T= 0 °C Patent; RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY; UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY; LAVOIE, Edmond, J.; PILCH, Daniel, S.; PARHI, Ajit; KAUL, Malvika; WO2010/127307; (2010); (A1) English View in Reaxys

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Rx-ID: 36298025 View in Reaxys 323/375 Yield

Conditions & References

227 mg

E E

HO O

Rx-ID: 3139665 View in Reaxys 324/375 Yield

Conditions & References

74 %

With sodium tetrahydroborate in methanol Yamada, Fumio; Hasegawa, Toshifumi; Wakita, Masayuki; Sugiyama, Mitsuru; Somei, Masanori; Heterocycles; vol. 24; nb. 5; (1986); p. 1223 - 1226 View in Reaxys

62 %

With sodium tetrahydroborate in methanol, Time= 0.5h, T= 20 °C Somei, Masanori; Yamada, Fumio; Heterocycles; vol. 74; nb. C; (2007); p. 943 - 950 View in Reaxys O

N N

Rx-ID: 34059527 View in Reaxys 325/375 Yield

O N

O O

Rx-ID: 305118 View in Reaxys 326/375 Yield

Conditions & References With sodium tetrahydroborate, ethanol

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Shechter et al.; Journal of the American Chemical Society; vol. 78; (1956); p. 4984,4985 View in Reaxys With tetrahydrofuran, diethyl ether, boric acid trimethyl ester, sodium Shechter et al.; Journal of the American Chemical Society; vol. 78; (1956); p. 4984,4985 View in Reaxys With sodium hydroxide, sodium tetrahydroborate in ethanol, Time= 2h, T= 0 - 5 °C Meyers,A.I.; Sircar,J.C.; Journal of Organic Chemistry; vol. 32; (1967); p. 4134 - 4136 View in Reaxys With sodium hydroxide, sodium tetrahydroborate in water, acetonitrile, Time= 2h, T= 0 - 5 °C Meyers,A.I.; Sircar,J.C.; Journal of Organic Chemistry; vol. 32; (1967); p. 4134 - 4136 View in Reaxys F

F F

F O

F F

Rx-ID: 38266870 View in Reaxys 327/375 Yield

F F

F O

F F

F O

F F

Rx-ID: 38266871 View in Reaxys 328/375 Yield

Rx-ID: 27729426 View in Reaxys 329/375 Yield 55 %

Conditions & References 2 :To a suspension of sodium borohydride (1.52 g, 40 mmol) in ethanol (20 ml) at 0°C was added a solution of 208 (6 g, 20 mmol) in THF (40 ml). The addition was over 20 min, the reaction mixture was stirred for 1 h at 0 °C and at rt for 30 min. 2M HCl (20 ml) was added (care - vigorous reaction.) and ethyl acetate (100 ml). The layers were separated and the aqueous layer was extracted with ethyl acetate (2 x 60 ml). The combined organic layers were washed with water (60 ml) and brine (60 ml), dried (MgSO4) and concentrated in vacuo to afford the crude material as an orange oil. Purification by flash column chromatography eluting with hex:EtOAc; 4:1 afforded the title compound (3.35 g, 55percent) as a pale green solid. 1H NMR (270 MHz; CDCl3) 1.44 (3H, d, J- 6.7 Hz, CH3), 2.87 (IH, dd, J= 14.1, 6.9 Hz, one of CH2), 3.19 (IH, dd, J 14.I5 7.4 Hz, one of CH2), 3.85 (3H5 s, OCH3), 4.65 (IH5 sext, J= 6.9 Hz5

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CH), 5.12 (2H5 s, CH2Ph)5 6.65-6.71 (2H5 m, 2 x CH)56.81 (IH5 d5 J= 8.2 Hz, CH)5 7.25-7.43 (5H, m, 5 x CH). 13C NMR (67.5 MHz; CDCl3) 18.71 (CH3), 40.80 (CH2), 56.08 (OCH3), 71.17 (CH2), 84.64 (CH)5 112.0 (CH), 115.15 (CH)5 121.93 (CH)5 127.47 (CH), 127.87 (C)5 128.0 (CH)5 128.67 (CH)5 136.99 (C)5 148.14 (C)5 149.13 (C)5 LC/MS (APCI-) V = 1.1 min, m/z 300.01 (M-H)". Stage 1: With sodium tetrahydroborate in tetrahydrofuran, ethanol, Time= 1.83333h, T= 0 - 20 °C Stage 2: With hydrogenchloride, water in tetrahydrofuran, ethanol, ethyl acetate Patent; STERIX LIMITED; WO2008/117061; (2008); (A2) English View in Reaxys 55 %

With sodium tetrahydroborate in tetrahydrofuran, ethanol, Time= 2h, T= 0 - 20 °C Leese, Mathew P.; Jourdan, Fabrice; Dohle, Wolfgang; Kimberley, Meriel R.; Thomas, Mark P.; Bai, Ruoli; Hamel, Ernest; Ferrandis, Eric; Potter, Barry V. L.; ACS Medicinal Chemistry Letters; vol. 3; nb. 1; (2012); p. 5 - 9 View in Reaxys

55 %

With sodium tetrahydroborate in tetrahydrofuran, ethanol, Time= 2h, T= 0 - 20 °C Dohle, Wolfgang; Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Bai, Ruoli; Hamel, Ernest; Ferrandis, Eric; Kasprzyk, Philip G.; Fiore, Ann; Newman, Simon P.; Purohit, Atul; Potter, Barry V. L.; ChemMedChem; vol. 9; nb. 2; (2014); p. 350 - 370 View in Reaxys O

O N

Rx-ID: 34059499 View in Reaxys 330/375 Yield

Conditions & References Reaction Steps: 3 1: sodium tetrahydroborate / methanol / 1.5 h / 20 °C / |Inert atmosphere 2: 10 Pd/C; hydrogen / methanol / |Inert atmosphere 3: water / 18 h / 20 °C / |Inert atmosphere With sodium tetrahydroborate, 10 Pd/C, hydrogen in methanol, water, 3: |Mannich Aminomethylation Anderson, James C.; Noble, Adam; Torres, Pascual Ribelles; Tetrahedron Letters; vol. 53; nb. 42; (2012); p. 5707 - 5710 View in Reaxys

O N

Rx-ID: 2062727 View in Reaxys 331/375 Yield

Conditions & References With NSC26899 in acetonitrile, T= 80 °C , Yield given Tintillier, P.; Dupas, G.; Bourguignon, J.; Queguiner, G.; Tetrahedron Letters; vol. 27; nb. 21; (1986); p. 2357 2360 View in Reaxys

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O O

N O

O O

Rx-ID: 27729461 View in Reaxys 332/375 Yield

Conditions & References

62 %

Finely powdered sodium borohydride (3.38 g, 89.3 mmol) was covered with THF (40 mL) and ethanol (40 mL) and cooled to 0 0C. 257 (13.95 g, 44.5 mmol) was dissolved in THF (120 mL) and added slowly over 2 h via dropping funnel. The reaction mixture was stirred for 4 h at 0 °C and then for 60 h at room temperature. Hydrochloric acid (2M, 45 mL) was added very carefully. The two layers were separated and the organic layer was concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2: 100 g, hexane/ethyl acetate 90:10) to give the title compound (8.83 g, 62percent) as yellow solid. 1H NMR (270 MHz, CDCl3) δ 0.91 (3H, t, J 7.4, CH2CH3), 1.62-1.79 (1η, m, one of CHCH2CH3), 1.81-2.00 (IH, m, one of CHCH2CH3), 2.88 (IH, dd, J 14.3, 6.0, one of ArCH2CH), 3.12 (IH, dd, J 14.3, 8.3, one Of ArCH2CH), 3.84 (3H, s, OCH3), 4.42-4.55 <n="163"/>(IH, m, CHNO2), 5.11 (2H5 OCH2Ph), 6.65 (IH5 d, J 1.9, CH)5 6.69 (IH5 dd, J 8.2, 1.9,CH)5 6.80 (IH, d, J 8.0, CH)5 7.25-7.45 (5H, m, OCH2C6H5). ' With sodium tetrahydroborate in tetrahydrofuran, ethanol, Time= 66h, T= 0 - 20 °C Patent; STERIX LIMITED; WO2008/117061; (2008); (A2) English View in Reaxys

O O

E N

O O

Rx-ID: 37489935 View in Reaxys 333/375 Yield

Conditions & References

62 %

With sodium tetrahydroborate in tetrahydrofuran, ethanol, Time= 66h, T= 0 - 20 °C Dohle, Wolfgang; Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Bai, Ruoli; Hamel, Ernest; Ferrandis, Eric; Kasprzyk, Philip G.; Fiore, Ann; Newman, Simon P.; Purohit, Atul; Potter, Barry V. L.; ChemMedChem; vol. 9; nb. 2; (2014); p. 350 - 370 View in Reaxys O

O O

N N F F

Rx-ID: 34059524 View in Reaxys 334/375 Yield

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N F F

Rx-ID: 34059534 View in Reaxys 335/375 Yield

Rx-ID: 34059532 View in Reaxys 336/375 Yield

O N

O N O

HO O HO

O HO

Rx-ID: 20174882 View in Reaxys 337/375 Yield

Conditions & References Reaction Steps: 3 1: NaBH4 / ethanol / 24 h / Ambient temperature 2: CdCO3 / toluene / 24 h / Heating 3: 38 mg / 5 percent KOH / methanol / 24 h / Ambient temperature With potassium hydroxide, sodium tetrahydroborate, anhydrous cadmium carbonate in methanol, ethanol, toluene Ina, Hiroji; Iida, Hideo; Chemical and Pharmaceutical Bulletin; vol. 34; (1986); p. 726 - 729 View in Reaxys

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O N

HO O

N HO

O OH

Rx-ID: 21441378 View in Reaxys 338/375 Yield

Conditions & References Reaction Steps: 3 1: sodium borohydride / ethanol 2: cadmium carbonate / toluene 3: 5percent KOH / methanol With potassium hydroxide, sodium tetrahydroborate, cadmium(II) carbonate in methanol, ethanol, toluene Iida; Kikuchi; Kobayashi; Ina; Tetrahedron Letters; vol. 21; nb. 8; (1980); p. 759 - 760 View in Reaxys

O N

HO O

N HO

O OH

Rx-ID: 21441379 View in Reaxys 339/375 Yield

O O

N Br

Rx-ID: 34059525 View in Reaxys 340/375 Yield

O O

N Br

Rx-ID: 34059536 View in Reaxys 341/375

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Yield

O N

N O

Rx-ID: 15504367 View in Reaxys 342/375 Yield

Conditions & References Reaction Steps: 2 1: 92 percent / NaBH4; silica gel / propan-2-ol; CHCl3 / 0.67 h 2: 1.7 percent / AlCl3 / 18 h / 5 °C With sodium tetrahydroborate, aluminium trichloride, silica gel in chloroform, isopropyl alcohol Kilway, Kathleen V; Siegel, Jay S; Tetrahedron; vol. 57; nb. 17; (2001); p. 3615 - 3627 View in Reaxys O

Cl F

F F

Rx-ID: 33368900 View in Reaxys 343/375 Yield 50 %

Conditions & References D21 : D21: l-chloro-4-(4-(2-nitroethyl)phenoxy)-2-(trifluoromethyl)benzene D21: l-chloro-4-(4-(2-nitroethyl)phenoxy)-2-(trifluoromethyl)benzeneTo a suspension of (E)-l -chloro-4-(4-(2-nitrovinyl)phenoxy)-2-(trifluoromethyl)benzene (13 g, 43.2 mmol) and silica gel (120 g, 100-200 Mesh) in i-PrOH (155 mL) and CHC13 (465 mL), was added NaBH4 (13.65 g, 361 mmol) portionwise. The reaction mixture was stirred overnight at rt, filtered, and washed with DCM (1 L). The organic phase was washed with sat. NaHC03 (200 mL), then brine, and dried over anhydrous Na2S04 and concentrated to afford the title compound as a brown liquid (26 g, 50 percent yield).LC-MS (ESI): No MS signal, 1.70 min (ret time). Stage 1: With sodium tetrahydroborate in chloroform, isopropyl alcohol, T= 20 °C , Molecular sieve Stage 2: With sodium hydrogencarbonate in dichloromethane, chloroform, isopropyl alcohol Patent; GLAXO GROUP LIMITED; WAN, Zehong; LONG, Kai; ZHANG, Xiaomin; YU, Haihua; WO2013/14185; (2013); (A1) English View in Reaxys

50 %

21 : D21: 1-chloro-4-(4-(2-nitroethyl)phenoxy)-2-(trifluoromethyl)benzene D21: 1-chloro-4-(4-(2-nitroethyl)phenoxy)-2-(trifluoromethyl)benzene To a suspension of (E)-1-chloro-4-(4-(2-nitrovinyl)phenoxy)-2-(trifluoromethyl)benzene (13 g, 43.2 mmol) and silica gel (120 g, 100-200 Mesh) in i-PrOH (155 mL) and CHCl3 (465 mL), was added NaBH4 (13.65 g, 361 mmol) portionwise. The reaction mixture was stirred overnight at rt, filtered, and washed with DCM (1 L).

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The organic phase was washed with sat. NaHCO3 (200 mL), then brine, and dried over anhydrous Na2SO4 and concentrated to afford the title compound as a brown liquid (26 g, 50percent yield). LC-MS (ESI): No MS signal, 1.70 min (ret time). With sodium tetrahydroborate, isopropyl alcohol in chloroform, T= 20 °C Patent; Glaxo Group Limited; Long, Kai; Wan, Zehong; US2013/30012; (2013); (A1) English View in Reaxys 50 %

D.21 : 1-chloro-4-(4-(2-nitroethyl)phenoxy)-2-(trifluoromethyl)benzene To a suspension of (E)-1-chloro-4-(4-(2-nitrovinyl)phenoxy)-2-(trifluoromethyl)benzene (13 g, 43.2 mmol) and silica gel (120 g, 100-200 Mesh) in i-PrOH (155 mL) and CHCl3 (465 mL), was added NaBH4 (13.65 g, 361 mmol) portionwise. The reaction mixture was stirred overnight at rt, filtered, and washed with DCM (1 L). The organic phase was washed with sat. NaHCO3 (200 mL), then brine, and dried over anhydrous Na2SO4 and concentrated to afford the title compound as a brown liquid (26 g, 50percent yield). With sodium tetrahydroborate in chloroform, isopropyl alcohol, T= 20 °C Patent; Wan, Zehong; Long, Kai; Zhang, Xiaomin; Yu, Haihua; US2014/179716; (2014); (A1) English View in Reaxys

49.2 %

D28: Chloro-4-(4-(2-nitroet enzeneTo the solution of (.pound.)-l-chloro-4-(4-(2-nitrovinyl)phenoxy)-2-(trifluoromethyl)benzene (640 mg, 1.862 mmol) in 2-pentanol (5 mL) and chloroform (15.00 mL) was added silica-gel (2g), and then NaBH4 (282 mg, 7.45 mmol). The reaction mixture was stirred at rt for 3 h. The mixture was purified via a flash column affording the title compound (330 mg, 49.2 percent yield). LCMS: rt=4.62 min, [M+H+] =NA With sodium tetrahydroborate, methyl propyl carbinol, silica gel in chloroform, Time= 3h, T= 20 °C Patent; GLAXO GROUP LIMITED; JIN, Yun; WAN, Zehong; ZHANG, Qing; WO2012/76435; (2012); (A1) English View in Reaxys

O N

O B

O O

Rx-ID: 10156659 View in Reaxys 344/375 Yield

Conditions & References With RhCl(PPh3)3 Vogels, Christopher M.; Decken, Andreas; Westcott, Stephen A.; Tetrahedron Letters; vol. 47; nb. 14; (2006); p. 2419 - 2422 View in Reaxys

O N

N O

racemate

Rx-ID: 4529283 View in Reaxys 345/375 Yield

Conditions & References With hydrogenchloride, sodium tetrahydroborate, 1.) benzene, MeOH, RT, 10 min, 2.) benzene, MeOH, RT, 5 min, Yield given. Multistep reaction. Yields of byproduct given Somei, Masanori; Yamada, Fumio; Yamazaki, Yoshihisa; Shinkura, Akiko; Chemical and Pharmaceutical Bulletin; vol. 44; nb. 1; (1996); p. 21 - 28 View in Reaxys

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With hydrogenchloride, sodium tetrahydroborate, 1.) dioxane, MeOH, RT, 10 min, 2.) dioxane, MeOH, RT, 5 min, Yield given. Multistep reaction. Yields of byproduct given Somei, Masanori; Yamada, Fumio; Yamazaki, Yoshihisa; Shinkura, Akiko; Chemical and Pharmaceutical Bulletin; vol. 44; nb. 1; (1996); p. 21 - 28 View in Reaxys

O N

Rx-ID: 17683086 View in Reaxys 346/375 Yield

Conditions & References Reaction Steps: 2 1: 87 percent / NaBH4 / methanol / 0.5 h / Ambient temperature 2: 80 percent / 1N aq. HCl / tetrahydrofuran / 3.5 h / 60 °C With hydrogenchloride, sodium tetrahydroborate in tetrahydrofuran, methanol Somei, Masanori; Yamada, Fumio; Yamazaki, Yoshihisa; Shinkura, Akiko; Chemical and Pharmaceutical Bulletin; vol. 44; nb. 1; (1996); p. 21 - 28 View in Reaxys O

racemate

Rx-ID: 4646640 View in Reaxys 347/375 Yield

Conditions & References

92 %

With sodium tetrahydroborate in tetrahydrofuran, water Hirai, Yoshimasa; Nagaoka, Hiroto; Tetrahedron Letters; vol. 38; nb. 11; (1997); p. 1969 - 1970 View in Reaxys

Rx-ID: 2608011 View in Reaxys 348/375 Yield 98 %

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 0.583333h, T= 25 °C Sinhababu, Achintya K.; Borchardt, Ronald T.; Tetrahedron Letters; vol. 24; nb. 3; (1983); p. 227 - 230 View in Reaxys Br O

Br O

E N

Rx-ID: 2592130 View in Reaxys 349/375

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Yield

Conditions & References

65 %

With sodium tetrahydroborate in diethylene glycol dimethyl ether, Time= 1h, T= 0 °C Nishiyama, Shigeru; Yamamura, Shosuke; Tetrahedron Letters; vol. 23; nb. 12; (1982); p. 1281 - 1284 View in Reaxys

Z Br

O N

Rx-ID: 2595067 View in Reaxys 350/375 Yield

Conditions & References

52.8 %

With sodium tetrahydroborate in methanol, Time= 2h, Ambient temperature Bhakuni, D. S.; Kumar, P.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 22; nb. 1; (1983); p. 5 - 8 View in Reaxys

E N

Rx-ID: 10451783 View in Reaxys 351/375 Yield

Conditions & References

80 %

With sodium tetrahydroborate in ethanol, Time= 2h, T= 0 °C Chandrasekhar; Reddy, N. Ramakrishna; Rao, Y. Srinivasa; Tetrahedron; vol. 62; nb. 51; (2006); p. 12098 12107 View in Reaxys

O O

O Si

Rx-ID: 12312640 View in Reaxys 352/375 Yield

Conditions & References Reaction Steps: 4 1: 100 percent / sodium borohydride; silica gel / CHCl3; propan-2-ol / 1.5 h / 20 °C 2: 95 percent / aq. HCl / methanol / 0.5 h / 20 °C 3: 96 percent / Dess-Martin periodinane / CH2Cl2 / 0.75 h / 20 °C 4: B(OH)3; H2O2; H2SO4 / tetrahydrofuran; H2O / 9 h / 20 °C With hydrogenchloride, sodium tetrahydroborate, sulfuric acid, dihydrogen peroxide, boric acid, silica gel, Dess-Martin periodane in tetrahydrofuran, methanol, dichloromethane, chloroform, water, isopropyl alcohol, 4: Dakin oxidation Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.; Organic Letters; vol. 8; nb. 15; (2006); p. 3243 3246 View in Reaxys

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O O O

N O

O O

Rx-ID: 20870357 View in Reaxys 353/375 Yield

Conditions & References Reaction Steps: 3 1: 92 percent / sodium borohydride / methanol; ethyl acetate / 0.25 h / 0 °C 2: 95 percent / hydrogen / PtO2 / acetic acid / 3 h / 760 Torr / Ambient temperature 3: 77 percent / methanol / 12 h / Ambient temperature With sodium tetrahydroborate, hydrogen, platinum(IV) oxide in methanol, acetic acid, ethyl acetate Andrew, Robert G.; Raphael, Ralph A.; Tetrahedron; vol. 43; nb. 21; (1987); p. 4803 - 4816 View in Reaxys

O N

Rx-ID: 3153115 View in Reaxys 354/375 Yield

Conditions & References

87 %

With sodium tetrahydroborate in methanol, Time= 0.5h, Ambient temperature Somei, Masanori; Yamada, Fumio; Yamazaki, Yoshihisa; Shinkura, Akiko; Chemical and Pharmaceutical Bulletin; vol. 44; nb. 1; (1996); p. 21 - 28 View in Reaxys

81 %

With sodium tetrahydroborate in methanol Yamada, Fumio; Hasegawa, Toshifumi; Wakita, Masayuki; Sugiyama, Mitsuru; Somei, Masanori; Heterocycles; vol. 24; nb. 5; (1986); p. 1223 - 1226 View in Reaxys

O O

O O Si

N O

Rx-ID: 12312639 View in Reaxys 355/375 Yield

Conditions & References Reaction Steps: 3 1: 100 percent / sodium borohydride; silica gel / CHCl3; propan-2-ol / 1.5 h / 20 °C 2: 95 percent / aq. HCl / methanol / 0.5 h / 20 °C 3: 96 percent / Dess-Martin periodinane / CH2Cl2 / 0.75 h / 20 °C With hydrogenchloride, sodium tetrahydroborate, silica gel, Dess-Martin periodane in methanol, dichloromethane, chloroform, isopropyl alcohol Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.; Organic Letters; vol. 8; nb. 15; (2006); p. 3243 3246 View in Reaxys

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O O O

N O

N H O

Rx-ID: 20870356 View in Reaxys 356/375 Yield

Conditions & References Reaction Steps: 3 1: 92 percent / sodium borohydride / methanol; ethyl acetate / 0.25 h / 0 °C 2: 95 percent / hydrogen / PtO2 / acetic acid / 3 h / 760 Torr / Ambient temperature 3: 1.) reflux, 2 h, 2.) reflux, 3 h With sodium tetrahydroborate, hydrogen, platinum(IV) oxide in methanol, acetic acid, ethyl acetate Andrew, Robert G.; Raphael, Ralph A.; Tetrahedron; vol. 43; nb. 21; (1987); p. 4803 - 4816 View in Reaxys

O O

O O O

N HO

Rx-ID: 12312641 View in Reaxys 357/375 Yield

Conditions & References Reaction Steps: 2 1: 100 percent / sodium borohydride; silica gel / CHCl3; propan-2-ol / 1.5 h / 20 °C 2: 95 percent / aq. HCl / methanol / 0.5 h / 20 °C With hydrogenchloride, sodium tetrahydroborate, silica gel in methanol, chloroform, isopropyl alcohol Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.; Organic Letters; vol. 8; nb. 15; (2006); p. 3243 3246 View in Reaxys O

N O

Rx-ID: 44820334 View in Reaxys 358/375 Yield 91.1 %

Conditions & References 3.4 : Synthesis of tert-butyl 4-(4-(2-nitroethyl)naphthalen-1-yl)piperazine-1-carboxylate A solution of 4- (4- (2-nitroethenyl) naphthalen-1-yl) piperazine-1-tert-butylcarboxylate (4.4 g, 11.48 mmol)Methanol / tetrahydrofuran (v / v = 5/1), cooled to 0 ° C in a low temperature bath and NaBH4 (1.16 g, 30.64 mmol) was slowly added. The reaction was completed at room temperature for 4 h. (DCM / MeOH (v / v) = 100/1) to give the title compound as a yellow solid (4.3 g, 91.1percent) by adding cold water to a quench reaction, dichloromethane (30 mL) and column chromatography. With sodium tetrahydroborate in tetrahydrofuran, methanol, Time= 4h, T= 0 - 20 °C Patent; Guangdong East Sunshine Pharmaceutical Co., Ltd.; Zhang, Yinjun; Jin, Chuanfei; Nei, Biao; Xu, jinghong; Cai, ShaoYu; (34 pag.); CN104230742; (2016); (B) Chinese View in Reaxys

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O O

Rx-ID: 8975820 View in Reaxys 359/375 Yield

N O O

Rx-ID: 1117003 View in Reaxys 360/375 Yield

Conditions & References With sodium hydroxide, sodium tetrahydroborate in water, acetonitrile, T= 0 - 5 °C Meyers,A.I.; Sircar,J.C.; Journal of Organic Chemistry; vol. 32; (1967); p. 4134 - 4136 View in Reaxys With sodium hydroxide, sodium tetrahydroborate in water, acetonitrile, T= 0 - 5 °C Meyers,A.I.; Sircar,J.C.; Journal of Organic Chemistry; vol. 32; (1967); p. 4134 - 4136 View in Reaxys

N O

Rx-ID: 31472544 View in Reaxys 361/375 Yield

Conditions & References

97 %

With sodium tetrahydroborate in methanol, dichloromethane, Time= 0.25h, Cooling with ice Lowell, Andrew N.; Fennie, Michael W.; Kozlowski, Marisa C.; Journal of Organic Chemistry; vol. 76; nb. 16; (2011); p. 6488 - 6502 View in Reaxys

O O

E O

O O

N O

Rx-ID: 25960479 View in Reaxys 362/375 Yield 83 %

Conditions & References With sodium tetrahydroborate in methanol, dichloromethane, Time= 0.5h Lowell, Andrew N.; Fennie, Michael W.; Kozlowski, Marisa C.; Journal of Organic Chemistry; vol. 73; nb. 5; (2008); p. 1911 - 1918 View in Reaxys

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H H

E O

Rx-ID: 39962445 View in Reaxys 363/375 Yield

Conditions & References Reaction Steps: 3 1: sodium tetrahydroborate / methanol 2: camphor-10-sulfonic acid / methanol / 50 °C 3: Dess-Martin periodane / dichloromethane With sodium tetrahydroborate, camphor-10-sulfonic acid, Dess-Martin periodane in methanol, dichloromethane Nagai, Satoka; Yamagishi, Yuka; Shimizu, Yuta; Takao, Ken-Ichi; Tadano, Kin-Ichi; Heterocycles; vol. 90; nb. 2; (2015); p. 819 - 826 View in Reaxys

H H

E O

Rx-ID: 39962444 View in Reaxys 364/375 Yield

Conditions & References Reaction Steps: 2 1: sodium tetrahydroborate / methanol 2: camphor-10-sulfonic acid / methanol / 50 °C With sodium tetrahydroborate, camphor-10-sulfonic acid in methanol Nagai, Satoka; Yamagishi, Yuka; Shimizu, Yuta; Takao, Ken-Ichi; Tadano, Kin-Ichi; Heterocycles; vol. 90; nb. 2; (2015); p. 819 - 826 View in Reaxys

O O

E O O Si

N O Si

Rx-ID: 12312643 View in Reaxys 365/375 Yield

Conditions & References Reaction Steps: 5 1: 100 percent / sodium borohydride; silica gel / CHCl3; propan-2-ol / 1.5 h / 20 °C 2: 95 percent / aq. HCl / methanol / 0.5 h / 20 °C 3: 96 percent / Dess-Martin periodinane / CH2Cl2 / 0.75 h / 20 °C 4: B(OH)3; H2O2; H2SO4 / tetrahydrofuran; H2O / 9 h / 20 °C 5: 196 mg / imidazole / CH2Cl2; dimethylformamide / 1 h / 20 °C

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With 1H-imidazole, hydrogenchloride, sodium tetrahydroborate, sulfuric acid, dihydrogen peroxide, boric acid, silica gel, Dess-Martin periodane in tetrahydrofuran, methanol, dichloromethane, chloroform, water, N,N-dimethyl-formamide, isopropyl alcohol, 4: Dakin oxidation Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.; Organic Letters; vol. 8; nb. 15; (2006); p. 3243 3246 View in Reaxys

Rx-ID: 4129294 View in Reaxys 366/375 Yield

Conditions & References With sodium borodeuteride in tetrahydrofuran, ethanol Rotman; Daly; Creveling; Journal of Labelled Compounds; vol. 11; nb. 3; (1975); p. 445 - 452 View in Reaxys

H H

H O HO

E O

N O

Rx-ID: 39962446 View in Reaxys 367/375 Yield

Conditions & References Reaction Steps: 4 1: sodium tetrahydroborate / methanol 2: camphor-10-sulfonic acid / methanol / 50 °C 3: Dess-Martin periodane / dichloromethane 4: tetrahydrofuran / -18 °C With sodium tetrahydroborate, camphor-10-sulfonic acid, Dess-Martin periodane in tetrahydrofuran, methanol, dichloromethane Nagai, Satoka; Yamagishi, Yuka; Shimizu, Yuta; Takao, Ken-Ichi; Tadano, Kin-Ichi; Heterocycles; vol. 90; nb. 2; (2015); p. 819 - 826 View in Reaxys

O O

O Si

Rx-ID: 10262943 View in Reaxys 368/375 Yield 100 %

Conditions & References With sodium tetrahydroborate, silica gel in chloroform, isopropyl alcohol, Time= 1.5h, T= 20 °C

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Waters, Stephen P.; Fennie, Michael W.; Kozlowski, Marisa C.; Organic Letters; vol. 8; nb. 15; (2006); p. 3243 3246 View in Reaxys

O N

O O

O O O

O O

Rx-ID: 20174883 View in Reaxys 369/375 Yield

Conditions & References Reaction Steps: 2 1: NaBH4 / ethanol / 24 h / Ambient temperature 2: CdCO3 / toluene / 24 h / Heating With sodium tetrahydroborate, anhydrous cadmium carbonate in ethanol, toluene Ina, Hiroji; Iida, Hideo; Chemical and Pharmaceutical Bulletin; vol. 34; (1986); p. 726 - 729 View in Reaxys

O N

O O

O O O

O O

Rx-ID: 20174884 View in Reaxys 370/375 Yield

O O O

N O

O O

Rx-ID: 21441380 View in Reaxys 371/375 Yield

Conditions & References Reaction Steps: 2 1: sodium borohydride / ethanol 2: cadmium carbonate / toluene With sodium tetrahydroborate, cadmium(II) carbonate in ethanol, toluene Iida; Kikuchi; Kobayashi; Ina; Tetrahedron Letters; vol. 21; nb. 8; (1980); p. 759 - 760 View in Reaxys

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O O

Rx-ID: 21441381 View in Reaxys 372/375 Yield

O N

N N

N O

Rx-ID: 45683018 View in Reaxys 373/375 Yield

Conditions & References

80 %

1.3 : TC642: 0.05 g of TC641 was dissolved in 3 mL of methanol and 0.038 g of sodium borohydride80115860) and stirred at room temperature for 1 hour. After the end of the reaction, the saturated ammonium chloride aqueous solution was quenched to separate the organic phase and the aqueous phaseDichloromethane was extracted three times, and the organic phase was combined, washed successively with saturated aqueous ammonium chloride solution and saturated brine, and then washed with anhydrousDried over sodium sulfate, filtered to remove sodium sulfate and concentrated to give the crude product. The crude product was purified by column chromatography (200-300 mesh silica gel, eluentFor dichloromethane: methanol = 15: 1) to give pure TC642. With methanol, sodium tetrahydroborate, Time= 1h, T= 20 °C Patent; ShanghaiTech University; Tao Houchao; Rui Mande·shidiwensi; Zhao Fei; Zhao Suwen; Xu Fei; (28 pag.); CN106831718; (2017); (A) Chinese View in Reaxys

O O

O E

O O

N O

Rx-ID: 31472619 View in Reaxys 374/375 Yield 0.54 g

Conditions & References Stage 1: With sodium tetrahydroborate in methanol, chloroform, Time= 0.0833333h Stage 2: With hydrogenchloride in methanol, chloroform, water, pH= 3 Lowell, Andrew N.; Fennie, Michael W.; Kozlowski, Marisa C.; Journal of Organic Chemistry; vol. 76; nb. 16; (2011); p. 6488 - 6502 View in Reaxys

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H H

H O

O O

E O

O O

N O

Rx-ID: 39962443 View in Reaxys 375/375 Yield 69 %

Conditions & References With sodium tetrahydroborate in methanol Nagai, Satoka; Yamagishi, Yuka; Shimizu, Yuta; Takao, Ken-Ichi; Tadano, Kin-Ichi; Heterocycles; vol. 90; nb. 2; (2015); p. 819 - 826 View in Reaxys

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