1-Benzofuran-5-carbaldehyde [C9H6O2]

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18 reactions in Reaxys

2017-10-28 12h:47m:02s (EST)

O

1. Query

O

Search as: As drawn

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O

O O

O

Rx-ID: 29109422 View in Reaxys 1/18 Yield 83 %

Conditions & References With N-Bromosuccinimide, 2,2'-azobis(isobutyronitrile) in chlorobenzene, Time= 1h, T= 80 °C Saitoh, Morihisa; Kunitomo, Jun; Kimura, Eiji; Iwashita, Hiroki; Uno, Yumiko; Onishi, Tomohiro; Uchiyama, Noriko; Kawamoto, Tomohiro; Tanaka, Toshimasa; Mol, Clifford D.; Dougan, Douglas R.; Textor, Garret P.; Snell, Gyorgy P.; Takizawa, Masayuki; Itoh, Fumio; Kori, Masakuni; Journal of Medicinal Chemistry; vol. 52; nb. 20; (2009); p. 6270 - 6286 View in Reaxys

75 %

4.2.50. (Z)-3-(Benzofuran-5-yl)acrylic acid (cis-52) NBS (0.656 g, 3.69 mmol) and AIBN (8.10 mg, 49.2 lmol) wereadded to a solution of 107 (0.364 g, 2.46 mmol) in chlorobenzene(7.3 mL) at room temperature under an argon atmosphere. Afterstirring for 1 h at 80 C, the mixture was cooled to room temperatureand diluted with EtOAc. The organic layers were washed withsaturated aqueous NaHCO3 and brine, dried (Na2SO4), filtered, andconcentrated in vacuo. The residue was purified by silica gel CC(EtOAc/hexane, 3:97) to afford benzofuran-5-carbaldehyde (108)(0.268 g, 1.84 mmol, 75percent) as a colorless oil: 1H-NMR (CDCl3,400 MHz) d: 6.82 (d, J = 2.0 Hz, 1H, furan-H), 7.54 (d, J = 8.8 Hz,1H, Ar–H), 7.65 (d, J = 2.0 Hz, 1H, furan-H), 7.79 (d, J = 8.8 Hz, 1H,Ar–H), 8.07 (s, 1H, Ar–H), 9.99 (s, 1H, –CHO); spectroscopic datawere consistent with those reported in the literature (van Otterloet al., 2005). With N-Bromosuccinimide, 2,2'-azobis(isobutyronitrile) in chlorobenzene, Time= 1h, T= 20 - 80 °C , Inert atmosphere Nishikawa, Keisuke; Fukuda, Hiroshi; Abe, Masato; Nakanishi, Kazunari; Taniguchi, Tomoya; Nomura, Takashi; Yamaguchi, Chihiro; Hiradate, Syuntaro; Fujii, Yoshiharu; Okuda, Katsuhiro; Shindo, Mitsuru; Phytochemistry; vol. 96; (2013); p. 132 - 147 View in Reaxys

60 %

Synthesis of Benzofuran-5-carbaldehyde To a solution of 2,3-dihydrobenzofuran-5-carbaldehyde (1 g, 6.75 mmol, A) in Chlorobenzene (20 mL), NBS (1.44 g, 8.10 mmol), AIBN (22 mg, 0.13 mmol) were added and the mixture was stirred at 80° C. for 1 h. After cooling the reaction mixture to room temperature, it was washed with aqueous NaHCO3. The organic layer was separated and the aqueous layer was washed with CH2Cl2. The organic layers were combined, dried over Na2SO4 and concentrated under vacuum on a rotary evaporator. The crude product was purified via gradient column chromatography using hexanes and ethyl acetate (100:1 to 1:1) to obtain the desired aldehyde B as brown syrup (60percent) which solidifies at 0° C. [0076] 1H NMR (500 MHz, CDCl3): δ 10.07 (s, 1H), 8.15 (d, J=1.2 Hz, 1H), 7.87 (dd, J=1.5, 8.6 Hz, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 6.90 (m, 1H). [0077] 13C NMR (125 MHz, CDCl3): δ 191.7, 158.2, 146.7, 132.2, 125.7, 124.6, 112.1, 107.2 With N-Bromosuccinimide, 2,2'-azobis(isobutyronitrile) in chlorobenzene, Time= 1h, T= 80 °C Patent; DUTTA, Aloke K.; US2014/309427; (2014); (A1) English View in Reaxys

O

O O

N

Rx-ID: 10701378 View in Reaxys 2/18 Yield 78 %

Conditions & References 20 :EXAMPLE 20 Preparation of 1-benzofuran-5-carbaldehyde To a solution of 1-benzofuran-5-carbonitrile (5.0 g, 34.9 mmol) in CH2Cl2 under nitrogen at -15 to -20° C. was added DIBAL-H (41.9 mL, 41.9 mmol, 1 M/heptane) and the temperature was maintained below -15° C. After addition was complete, the reaction mixture was stirred at -15 to -20° C. for an additional 10 min. The reaction mixture was quenched via dropwise addition of aqueous 2N HCl. The organic layer was separated and washed with water, dried over sodium sulfate, and concentrated to give 4.0 g (78percent) of 1-benzofuran-5-carbaldehyde as a yellow oil.

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Stage 1: With diisobutylaluminium hydride in n-heptane, dichloromethane, Time= 0.166667h, T= -20 - -15 °C Stage 2: With hydrogenchloride, water in n-heptane, dichloromethane Patent; Cole, Derek Cecil; Asselin, Magda; Boschelli, Diane Harris; Wissner, Allan; Wang, Yanong Daniel; Prashad, Amarnauth Shastrie; Dushin, Russell; US2007/287738; (2007); (A1) English View in Reaxys 78 %

15.a :EXAMPLE 15:PREPARATION OF 5-(5-FORMYL-I -BENZOFURAN-2-YL)-6-METHYL-4-[(4- METHYL-1 H-INDOL-5-YL)AMINO]NICOTINONITRILEStep a): Preparation of 5-formylbenzofuran.To a -150C to -2O0C solution of 1benzofuran-5-carbonitrile (5 g, 34.9 mmol) in 50 mL of dichloromethane under nitrogen was added DIBAL-H (41.9 mL, 41.9 mmol, 1.0M in heptane) such that the temperature was less than or equal to -150C. The reaction mixture was stirred for an additional 10 min at -150C to -2O0C and quenched by adding 2.0 N HCI dropwise such that the temperature was less than or equal to room temperature. The organic layer was then separated, washed with water, dried over sodium sulfate and concentrated to give 4 g (78percent) of the title compound as a yellow oil, which was used in the next step without further purification. Stage 1: With diisobutylaluminium hydride in n-heptane, dichloromethane, Time= 0.166667h, T= -20 - -15 °C Stage 2: With hydrogenchloride, water in n-heptane, dichloromethane, T= 20 °C Patent; WYETH; WO2009/76571; (2009); (A1) English View in Reaxys With diisobutylaluminium hydride in dichloromethane, Time= 0.166667h, T= -15 °C Prashad, Amar S.; Wang, Daniel; Subrath, Joan; Wu, Biqi; Lin, Melissa; Zhang, Mei-Yi; Kagan, Natasha; Lee, Julie; Yang, Xiaoke; Brennan, Agnes; Chaudhary, Divya; Xu, Xin; Leung, Louis; Wang, Jack; Boschelli, Diane H.; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 19; (2009); p. 5799 - 5802 View in Reaxys

O

N

O

Br

O

Rx-ID: 4607496 View in Reaxys 3/18 Yield 70 %

Conditions & References 1031 : Preparative Example 1031 A solution of 5-bromobenzofuran (950 mg, 4.82 [MMOL)] in anhydrous ether (12 mL) was cooled to-78 [°C.] 1.7 M [TELT-BULI] solution in pentane (6 [ML,] 10.2 [MMOL)] was added dropwise under argon. After addition, the mixture was stirred at-78 °C for 20 min, followed by addition of a mixture of DMF (0.8 mL) and ether (1 mL). The mixture was allowed to warm to rt and stirred for 0.5 h. Ethyl acetate was added. The mixture was poured to saturated ammonium chloride solution. The organic layer was separated and concentrated. The residue was purified by column chromatography (ethyl acetate-hexanes, 1: 5 [V/V)] to give the title compound as a pale yellow solid (490 mg, [70percent).] With tert.-butyl lithium in diethyl ether, pentane, Time= 0.833333h, T= -78 - 8 °C Patent; SCHERING CORPORATION; PHARMACOPEIA, INC.; WO2004/11418; (2004); (A1) English View in Reaxys

70 %

1031 :A solution of 5-bromobenzofuran (950 mg, 4.82 mmol) in anhydrous ether (12 mL) was cooled to-78 °C. 1.7 M tert-BuLi solution in pentane (6 ml, 10.2 mmol) was added dropwise under argon. After addition, the mixture was stirred at-78 °C for 20 min, followed by addition of a mixture of DMF (0.8 mL) and ether (1 mL). The mixture was allowed to warm to rt and stirred for 0.5 h. Ethyl acetate was added. The mixture was poured to saturated ammonium chloride solution. The organic layer was separated and concentrated. The residue was purified by column chromatography (ethyl acetate-hexanes, 1: 5 v/v) to give the title compound as a pale yellow solid (490 mg, 70percent). Stage 1: With tert.-butyl lithium in diethyl ether, pentane, Time= 0.333333h, T= -78 °C Stage 2: in diethyl ether, pentane, Time= 0.5h, T= -78 - 20 °C , Product distribution / selectivity Patent; SCHERING CORPORATION; PHARMACOPEIA DRUG DISCOVERY, INC.; WO2005/68460; (2005); (A1) English View in Reaxys

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67 %

34.4 : Preparative example34.4 To a solution of the product from Step B (2 g) in ether (20 ml) at -78 C. was added t-BuLi dropwise. After stirring for 20 min, DMF (950 mg) was added dropwise and the mixture was stirred at ?25 C. for 3 hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgSO4, filtered and concentrated in vacuo to give 980 mg of crude product (67percent). With ammonium chloride, tert.-butyl lithium in benzene, Time= 3h, T= -25 - 20 °C Patent; Schering Corporation; US2004/106794; (2004); (A1) English View in Reaxys

67 %

34.4.C :Step C; To a solution of the product from Step B (2g) in ether (20mut) at-78°C was added t-BuLi dropwise. After stirring for 20min, DMF (950mg) was added dropwise and the mixture was stirred at-25°C for 3hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgS04, filtered and concentrated in vacuo to give 980mg of crude product (67percent). Stage 1: With tert.-butyl lithium in diethyl ether, Time= 0.333333h, T= -78 °C Stage 2: in diethyl ether, T= -25 - 20 °C Patent; SCHERING CORPORATION; PHARMACOPEIA DRUG DISCOVERY, INC.; WO2005/66147; (2005); (A1) English View in Reaxys

67 %

34.4.C :To a solution of the product from Step B (2g) in ether (20ml) at-78°C was added t-BuLi dropwise. After stirring for 20min, DMF (950mg) was added dropwise and the mixture was stirred at-25°C for 3hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgS04, filtered and concentrated in vacuo to give 980mg of crude product (67percent). Stage 1: With tert.-butyl lithium in diethyl ether, Time= 0.333333h, T= -78 °C Stage 2: in diethyl ether, T= -25 - 20 °C , Product distribution / selectivity Patent; SCHERING CORPORATION; PHARMACOPEIA DRUG DISCOVERY, INC.; WO2005/68460; (2005); (A1) English View in Reaxys

54 %

1.IV : Step IV: [5-FOLMYL-L-BENZOFURAN] (Pla in scheme 2 for example [9) :] A mixture [OF 5-BROMO-1-BENZOFURAN (0. 5G),] Mg (0.92g, 0. [038MOL), I2] (1 crystal) in dry THF (2. [5ML)] under N2 atmosphere was refluxed for 30min. To this was added a solution of 5- [BROMO-1-BENZOFURAN] (4. [5G)] in 25mL of dry THF) as soon as [THE I2 COLOR] disappear and refluxed for another 2h. The reaction mixture was then cooled to-40°C and added dry DMF (3.6g) drop-wise and slowly warmed to RT for a period of 12h. The reaction mixture was then cooled to 0°C and acidified with 3N HCl to pH=2 and stirred for 30min. The reaction mixture was then diluted with water [(500ML),] extracted with ethylacetate [(2X200ML),] washed with brine and dried. The solvent was removed under vacuum and purified by column chromatography over silica gel (pet. [ETHER/ CH2CL2)] to give 5-formyl-1- [BENZOFURAN] (2g, 54percent) as a liquid. LC-MS: M/Z ESI: 1.47 min, [14734 (M +1).] Stage 1: With iodine, magnesium in tetrahydrofuran, Time= 2.5h, Heating / reflux Stage 2: in tetrahydrofuran, Time= 12h, T= -40 - 20 °C Patent; APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.; WO2004/7491; (2004); (A1) English View in Reaxys With tert.-butyl lithium, 1.) Et2O, -78 deg C, 2.) Et2O, Multistep reaction Tasker, Andrew S.; Sorensen, Bryan K.; Jae, Hwan-Soo; Winn, Martin; Von Geldern, Thomas W.; Dixon, Douglas B.; Chiou, William J.; Dayton, Brian D.; Calzadila, Samuel; Hernandez, Lisa; Marsh, Kennan C.; WuWong, J. Ruth; Opgenorth, Terry J.; Journal of Medicinal Chemistry; vol. 40; nb. 3; (1997); p. 322 - 330 View in Reaxys

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O

Rx-ID: 9907261 View in Reaxys 4/18 Yield

Conditions & References

50 %

With Grubb's 2nd generation catalyst in toluene, Time= 3h, T= 90 °C Van Otterlo, Willem A.L.; Morgans, Garreth L.; Madeley, Lee G.; Kuzvidza, Samuel; Moleele, Simon S.; Thornton, Natalie; De Koning, Charles B.; Tetrahedron; vol. 61; nb. 32; (2005); p. 7746 - 7755 View in Reaxys HO

O O O

Rx-ID: 12959016 View in Reaxys 5/18 Yield

Conditions & References Reaction Steps: 3 1: 89 percent / K2CO3 / acetone / 2 h / 60 °C 2: 82 percent / [RuClH(CO)(PPh3)3] / CH2Cl2 / 14 h / 65 °C 3: 50 percent / ((Mes)2C3H5N2)Cl2Ru=CHPh / toluene / 3 h / 90 °C With Grubb's 2nd generation catalyst, carbonylchlorohydridetris(triphenylphosphine) ruthenium(II), potassium carbonate in dichloromethane, acetone, toluene Van Otterlo, Willem A.L.; Morgans, Garreth L.; Madeley, Lee G.; Kuzvidza, Samuel; Moleele, Simon S.; Thornton, Natalie; De Koning, Charles B.; Tetrahedron; vol. 61; nb. 32; (2005); p. 7746 - 7755 View in Reaxys

O

O O

O

Rx-ID: 12959487 View in Reaxys 6/18 Yield

Conditions & References Reaction Steps: 4 1: 41 percent / 0.17 h / 250 °C / microwave irradiation 2: 89 percent / K2CO3 / acetone / 2 h / 60 °C 3: 82 percent / [RuClH(CO)(PPh3)3] / CH2Cl2 / 14 h / 65 °C 4: 50 percent / ((Mes)2C3H5N2)Cl2Ru=CHPh / toluene / 3 h / 90 °C With Grubb's 2nd generation catalyst, carbonylchlorohydridetris(triphenylphosphine) ruthenium(II), potassium carbonate in dichloromethane, acetone, toluene, 1: Claisen rearrangement Van Otterlo, Willem A.L.; Morgans, Garreth L.; Madeley, Lee G.; Kuzvidza, Samuel; Moleele, Simon S.; Thornton, Natalie; De Koning, Charles B.; Tetrahedron; vol. 61; nb. 32; (2005); p. 7746 - 7755 View in Reaxys O

O

Rx-ID: 12961917 View in Reaxys 7/18 Yield

Conditions & References Reaction Steps: 2 1: 82 percent / [RuClH(CO)(PPh3)3] / CH2Cl2 / 14 h / 65 °C

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2: 50 percent / ((Mes)2C3H5N2)Cl2Ru=CHPh / toluene / 3 h / 90 °C With Grubb's 2nd generation catalyst, carbonylchlorohydridetris(triphenylphosphine) ruthenium(II) in dichloromethane, toluene Van Otterlo, Willem A.L.; Morgans, Garreth L.; Madeley, Lee G.; Kuzvidza, Samuel; Moleele, Simon S.; Thornton, Natalie; De Koning, Charles B.; Tetrahedron; vol. 61; nb. 32; (2005); p. 7746 - 7755 View in Reaxys

O

n-nonyl halide

OH O

O

Rx-ID: 12965224 View in Reaxys 8/18 Yield

Conditions & References Reaction Steps: 5 1: K2CO3 / acetone 2: 41 percent / 0.17 h / 250 °C / microwave irradiation 3: 89 percent / K2CO3 / acetone / 2 h / 60 °C 4: 82 percent / [RuClH(CO)(PPh3)3] / CH2Cl2 / 14 h / 65 °C 5: 50 percent / ((Mes)2C3H5N2)Cl2Ru=CHPh / toluene / 3 h / 90 °C With Grubb's 2nd generation catalyst, carbonylchlorohydridetris(triphenylphosphine) ruthenium(II), potassium carbonate in dichloromethane, acetone, toluene, 2: Claisen rearrangement Van Otterlo, Willem A.L.; Morgans, Garreth L.; Madeley, Lee G.; Kuzvidza, Samuel; Moleele, Simon S.; Thornton, Natalie; De Koning, Charles B.; Tetrahedron; vol. 61; nb. 32; (2005); p. 7746 - 7755 View in Reaxys

O

O O 13 C H

HO 13 C H2

Rx-ID: 9904712 View in Reaxys 9/18 Yield

Conditions & References With manganese(IV) oxide in benzene, Time= 1.5h, Heating Janssen, C. G. M.; Verreet, B.; Lenoir, H. A. C.; Thijssen, J. B. A.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 47; nb. 4; (2004); p. 274 - 277 View in Reaxys

O

N

O

Rx-ID: 22957089 View in Reaxys 10/18 Yield 67 - 70 %

Conditions & References 34.4.C; 1031 : STEP C To a solution of the product from Step B (2g) in ether (20MI) AT-78°C was added t-BuLi dropwise. After stirring for 20min, DMF (950mg) was added dropwise and the mixture was stirred AT-25°C for 3hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MGS04, filtered and concentrated in vacuo to give 980mg of crude product (67percent); A solution of 5-bromobenzofuran (950 mg, 4.82 MMOL) in anhydrous ether (12 mL) was cooled to-78 °C. 1.7 M TERT-BULI solution in pentane (6 mi, 10.2 MMOL) was added dropwise under argon. After addition, the mixture was stirred at-78 °C for 20 min, followed by addition of a mixture of DMF (0.8 mL) and ether (1 mL). The mixture was allowed to warm to rt and stirred for 0.5 h. Ethyl acetate was added. The mixture was poured to saturated ammonium chloride solution. The organic layer was separated and concentrated. The residue was purified by column chromatography (ethyl acetate-hexanes, 1: 5 V/V) to give the title compound as a pale yellow solid (490 mg, 70percent). Stage 1: With tert.-butyl lithium in diethyl ether, Time= 0.333333h, T= -78 °C Stage 2: in diethyl ether, Time= 3h, T= -25 - 20 °C

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Patent; PHARMACOPEIA, INC.; WO2004/33440; (2004); (A1) English View in Reaxys 67 %

34.4.C : Step C To a solution ol the product from Step B (2 g) in ether (20 ml) at -78 C. was added t-BuLi dropwise. Alter stirring lor 20 min, DMF (950 mg) was added dropwise and the mixture was stirred at -25 C. lor 3 hrs and then warmed to room temperature overnight. Saturated ammonium chloride was added and the solution was extracted with ether. The ether layer was washed with brine, dried with MgSO4, filtered and concentrated in vacuo to give 980 mg ol crude product (67percent). Stage 1: With tert.-butyl lithium in diethyl ether, Time= 0.333333h, T= -78 °C Stage 2: in diethyl ether, T= -25 - 20 °C Patent; Schering Corporation and Pharmacopeia, Inc.; US2004/147559; (2004); (A1) English View in Reaxys

O Br

isobutyl halide

OH

O

Rx-ID: 17415334 View in Reaxys 11/18 Yield

Conditions & References Reaction Steps: 3 1: 1.) NaH / 1.) DMF, 0 deg C, 2.) DMF 2: polyphosphoric acid / benzene / Heating 3: 1.) t-BuLi / 1.) Et2O, -78 deg C, 2.) Et2O With PPA, tert.-butyl lithium, sodium hydride in benzene Tasker, Andrew S.; Sorensen, Bryan K.; Jae, Hwan-Soo; Winn, Martin; Von Geldern, Thomas W.; Dixon, Douglas B.; Chiou, William J.; Dayton, Brian D.; Calzadila, Samuel; Hernandez, Lisa; Marsh, Kennan C.; WuWong, J. Ruth; Opgenorth, Terry J.; Journal of Medicinal Chemistry; vol. 40; nb. 3; (1997); p. 322 - 330 View in Reaxys

O

Br

O O

O

Rx-ID: 17426326 View in Reaxys 12/18 Yield

Conditions & References Reaction Steps: 2 1: polyphosphoric acid / benzene / Heating 2: 1.) t-BuLi / 1.) Et2O, -78 deg C, 2.) Et2O With PPA, tert.-butyl lithium in benzene Tasker, Andrew S.; Sorensen, Bryan K.; Jae, Hwan-Soo; Winn, Martin; Von Geldern, Thomas W.; Dixon, Douglas B.; Chiou, William J.; Dayton, Brian D.; Calzadila, Samuel; Hernandez, Lisa; Marsh, Kennan C.; WuWong, J. Ruth; Opgenorth, Terry J.; Journal of Medicinal Chemistry; vol. 40; nb. 3; (1997); p. 322 - 330 View in Reaxys

O

Rx-ID: 4096024 View in Reaxys 13/18 Yield 58 %

Conditions & References With N,N,N',N',N'',N''-hexamethylphosphoric triamide, lithium chloride, Time= 1.5h, T= 130 °C Hiroya, Kou; Hashimura, Kazuya; Ogasawara, Kunio; Heterocycles; vol. 38; nb. 11; (1994); p. 2463 - 2472 View in Reaxys

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HO

O

Rx-ID: 18049027 View in Reaxys 14/18 Yield

Conditions & References Reaction Steps: 4 1: 85 percent / ethyldiisopropylamine / CH2Cl2 / 0.67 h / -78 - 20 °C 2: 88 percent / Pd(PPh3)2Cl2, Et3N / dimethylformamide / 1.5 h / 90 °C 3: 68 percent / K2CO3 / methanol / 8.5 h / Ambient temperature 4: 58 percent / LiCl, HMPA / 1.5 h / 130 °C With N,N,N',N',N'',N''-hexamethylphosphoric triamide, bis-triphenylphosphine-palladium(II) chloride, potassium carbonate, triethylamine, N-ethyl-N,N-diisopropylamine, lithium chloride in methanol, dichloromethane, N,N-dimethylformamide Hiroya, Kou; Hashimura, Kazuya; Ogasawara, Kunio; Heterocycles; vol. 38; nb. 11; (1994); p. 2463 - 2472 View in Reaxys

O

Si

O O

Rx-ID: 18072454 View in Reaxys 15/18 Yield

Conditions & References Reaction Steps: 2 1: 68 percent / K2CO3 / methanol / 8.5 h / Ambient temperature 2: 58 percent / LiCl, HMPA / 1.5 h / 130 °C With N,N,N',N',N'',N''-hexamethylphosphoric triamide, potassium carbonate, lithium chloride in methanol Hiroya, Kou; Hashimura, Kazuya; Ogasawara, Kunio; Heterocycles; vol. 38; nb. 11; (1994); p. 2463 - 2472 View in Reaxys

O F

F

S F

O

Rx-ID: 18076640 View in Reaxys 16/18 Yield

Conditions & References Reaction Steps: 3 1: 88 percent / Pd(PPh3)2Cl2, Et3N / dimethylformamide / 1.5 h / 90 °C 2: 68 percent / K2CO3 / methanol / 8.5 h / Ambient temperature 3: 58 percent / LiCl, HMPA / 1.5 h / 130 °C With N,N,N',N',N'',N''-hexamethylphosphoric triamide, bis-triphenylphosphine-palladium(II) chloride, potassium carbonate, triethylamine, lithium chloride in methanol, N,N-dimethyl-formamide Hiroya, Kou; Hashimura, Kazuya; Ogasawara, Kunio; Heterocycles; vol. 38; nb. 11; (1994); p. 2463 - 2472 View in Reaxys

O Br

O O

Rx-ID: 24438212 View in Reaxys 17/18 Yield

Conditions & References 31.C : Step C Step C Preparation of 5-formylbenzofuran

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A slurry of powdered magnesium (11.44 g) and iodine (0.12 g) in THF (120 mL) was heated to 50° C. under a N2 blanket for 0.5 hr. A 30 mL portion of the material prepared above in Example 31, Step B (90 g) in THF (225 mL) was then added at 50° C., without stirring. This mixture was aged for 0.5 hr and the the remaining 195 mL of the THF solution was added over 1.5 hr (with stirring) while maintaining a gentle reflux. When the addition was complete, the mixture was aged at 50° C. for 1 hr and then was cooled to 5° C. before DMF (45 mL) was added dropwise over 30 min while maintaining the reaction temperature between 5°-10° C. The mixture was then aged at 10° C. for 1 hr and then cooled to 5° C. before a mixture of 3N HCl (300 mL) and a 50percent sat. solution of brine (225 mL) was added while maintaining the reaction temperature below 15° C. The pH was also monitored and when the pH of the aqueous layer had fallen to 6, EtOAc (200 mL) was added and the remaining 3N HCl/brine mixture was added (final pH approx. 1.2). This mixture was stirred for 1 hr and the aqueous layer was removed and extracted with EtOAc (150 mL). The combined organic layers were washed successively with 2N HCl (100 mL) and brine (3*80 mL), dried over Na2 SO4, filtered and evaporated to dryness to give 63.6 g of the title compound as an orange oil that was of sufficient purity for use in the next step. With hydrogenchloride, iodine, magnesium in tetrahydrofuran, ethyl acetate, N,N-dimethyl-formamide Patent; Merck and Co., Inc.; US5229381; (1993); (A1) English View in Reaxys 1.d : Example 1 d) Benzo[b]furan-5-carboxaldehyde was prepared from 5-bromobenzo[b]furan (prepared from 4-bromophenol and bromoacetaldehyde diethyl acetal by the general method described in J. Chem. Soc. Perkin 1, 1972, 556) following essentially the same procedure as that described in b) above. Benzo[b]furan-5-carboxaldehyde was obtained as an oil. Pmr spectrum (CDCl3; δ in ppm): 6.90 (1H,d); 7.55-7.93 (3H,m); 8.15 (1H,d); 10.08 (1H,s). Patent; ICI AUSTRALIA LIMITED; EP125059; (1991); (B1) English View in Reaxys

O

O Br

O

OH

Br

O

Br

Rx-ID: 25040532 View in Reaxys 18/18 Yield

Conditions & References 1.d : EXAMPLE 1 (d) benzo[b]furan-5-carboxaldehyde was prepared from 5-bromobenzo[b]furan (prepared from 4-bromophenol and bromoacetaldehyde diethyl acetal by the general method described in J. Chem. Soc. Perkin 1, 1972, 556) following essentially the same procedure as that described in (b) above. Benzo[b]furan-5-carboxaldehyde was obtained as an oil. Pmr spectrum (CDCl3; δ in ppm): 6.90 (1H, d); 7.55-7.93 (3H, m); 8.15 (1H, d); 10.08 (1H, s). Patent; ICI Australia Limited; US4664693; (1987); (A1) English View in Reaxys

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