5-Pentyl-1,3-benzenediol (Olivetol) [C11H16O2] by Asch

Query Query

Results

Date

70 reactions in Reaxys

2018-02-18 00h:25m:16s (EST)

70 reactions in Reaxys

2018-02-18 00h:27m:47s (EST)

1. Query OH

Search as: As drawn 2. Query

(1. Query) AND NOT itemno in (6,7)

1/26

2018-02-18 01:17:24

Rx-ID: 271814 View in Reaxys 1/70 Yield 92 %

Conditions & References 1,3-Dihydroxy-5-alkylbenzenes (3, 4, 5): general method General procedure: To the solution of 1,3-dimethoxy-5-alkylbenzenes 8, 11, and 12,respectively, in dry dichloromethane was added dropwise 2.2 eq. of BBr3 (1 M solution in dichloromethane) at 15 °C and the reaction was stirred under argon atmosphere with temperature rising to r.t. over 1.5 h. The mixture was quenched with water, neutralized with NaHCO3 and extracted with dichloromethane. The organic phase was washed with water and brine and dried over MgSO4. After concentration in vacuo, the crude product was purified by silica gel column chromatography with petrol ether:ethyl acetate (9:1) as an eluent. The yields were 92percent for olivetol (3), 82percent for grevillol (4), and 86percent for cardol (adipostatin A, 6), respectively. With boron tribromide in dichloromethane, Time= 1.5h, T= -15 - 20 °C , Inert atmosphere Sisa, Miroslav; Dvorakova, Marcela; Vanek, Tomas; Tetrahedron; vol. 73; nb. 35; (2017); p. 5297 - 5301 View in Reaxys

81 %

With hydrogen bromide, acetic acid, Time= 3h, Heating Alonso, Emma; Ramon, Diego J.; Yus, Miguel; Journal of Organic Chemistry; vol. 62; nb. 2; (1997); p. 417 - 421 View in Reaxys

61 %

With lithium, ethylenediamine in tetrahydrofuran, Time= 14h, T= 8 °C Shindo, Takeyuki; Fukuyama, Yasuaki; Sugai, Takeshi; Synthesis; nb. 5; (2004); p. 692 - 700 View in Reaxys With hydrogen iodide Asahina; Chemische Berichte; vol. 69; (1936); p. 1643,1644 View in Reaxys Asahina; Nogami; Chemische Berichte; vol. 68; (1935); p. 1500,1501, 2392; Yakugaku Zasshi; vol. 55; (1935); p. 933,944 View in Reaxys With phosphorus, hydrogen iodide Asahina; Chemische Berichte; vol. 69; (1936); p. 1643,1644 View in Reaxys Asahina; Nogami; Chemische Berichte; vol. 68; (1935); p. 1500,1501, 2392; Yakugaku Zasshi; vol. 55; (1935); p. 933,944 View in Reaxys With pyridine, hydrogenchloride Petrzilka,T. et al.; Helvetica Chimica Acta; vol. 52; nb. 4; (1969); p. 1102 - 1134 View in Reaxys With pyridine hydrochloride, boron tribromide in dichloromethane, Time= 24h, T= -78 °C Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys With chloro-trimethyl-silane, sodium iodide in acetonitrile, Time= 36h, Heating Ayer, William A.; Browne, Lois M.; Lovell, Sarah H.; Phytochemistry (Elsevier); vol. 22; nb. 10; (1983); p. 2267 2272 View in Reaxys

2/26

2018-02-18 01:17:24

OH Cl

Rx-ID: 338558 View in Reaxys 2/70 Yield

Conditions & References T= 210 - 230 °C Adams; Hunt; Clark; Journal of the American Chemical Society; vol. 62; (1940); p. 735,737 View in Reaxys HO OH

OH O OH

Rx-ID: 384477 View in Reaxys 3/70 Yield

Conditions & References With sodium hydroxide Anker; Cook; Journal of the Chemical Society; (1945); p. 311 View in Reaxys With sodium hydroxide Korte,F.; Sieper,H.; Justus Liebigs Annalen der Chemie; vol. 630; (1960); p. 71 - 83 View in Reaxys With sodium hydroxide in water, Heating Kato,T.; Hozumi,T.; Chemical and Pharmaceutical Bulletin; vol. 20; (1972); p. 1574 - 1578 View in Reaxys O OH

Rx-ID: 1061698 View in Reaxys 4/70 Yield

Conditions & References With N,N-dimethyl-formamide Chandrasekharan,V. et al.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 16; (1978); p. 970 - 972 View in Reaxys O OH

OH O

Rx-ID: 1342766 View in Reaxys 5/70 Yield

Conditions & References (i) CuBr2, DME, (ii) (heating in DMF), (iii) aq. NaOH, Multistep reaction Marmor,R.S.; Journal of Organic Chemistry; vol. 37; nb. 18; (1972); p. 2901 - 2904 View in Reaxys

3/26

2018-02-18 01:17:24

Rx-ID: 1673493 View in Reaxys 6/70 Yield

Conditions & References Yield given. Multistep reaction Kotnis, Atul S.; Tetrahedron Letters; vol. 32; nb. 29; (1991); p. 3441 - 3444 View in Reaxys H O

O O OH

O H

Rx-ID: 2554705 View in Reaxys 7/70 Yield

Conditions & References With sodium hydroxide in methanol, water Chan, T. H.; Chaly, T.; Tetrahedron Letters; vol. 23; nb. 29; (1982); p. 2935 - 2938 View in Reaxys

O O

Rx-ID: 2964238 View in Reaxys 8/70 Yield

Conditions & References

48 %

With calcium carbonate in benzene, Time= 5h, Heating Jaxa-Chamiec, Albert A.; Sammes, Peter G.; Kennewell, Peter D.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 170 - 175 View in Reaxys

O OH

Rx-ID: 3487235 View in Reaxys 9/70 Yield 81 %

Conditions & References With sodium, butan-1-ol, Time= 1h, T= 80 - 90 °C Wu, Li-Qiang; Yang, Chun-Guang; Yang, Li-Ming; Yang, Li-Juan; Journal of Chemical Research; nb. 3; (2009); p. 183 - 185 View in Reaxys With hydrogen, palladium on activated charcoal in ethanol, Yield given Anand; Ranjan; Bulletin of the Chemical Society of Japan; vol. 56; nb. 6; (1983); p. 1889 - 1890

4/26

2018-02-18 01:17:24

View in Reaxys

Rx-ID: 6189901 View in Reaxys 10/70 Yield

Conditions & References

96%

16 : (FIG. 4A) Synthesis of Tri-deuterated Olivetol 26 Intermediate; Step e Scheme III (FIG. 4A) To a solution of bismethylolivetol 31 (4.0 g, 19.0 mmol) was added dropwise a solution of boron tribromide (32 mL, 1M, 32 mmol) in methylene chloride at -78° C. After addition, the reaction mixture was stirred at -78° C. for 1 hour, then at 0° C. for 2 hours, and then at 23° C. overnight. The reaction was quenched with water at 0° C. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated on a rotavaporator. Chromatography of the dried material on a silica gel column with hexane-ether (3:1) offered olivetol-d3 26 (3.34 g), in 96percent yield. Patent; Synthetic Technology Corporation; US5292899; (1994); (A1) English View in Reaxys Focella; Teitel; Brossi; Journal of Organic Chemistry; vol. 42; nb. 21; (1977); p. 3456 - 3457 View in Reaxys Patent; Hoffmann-La Roche; DE2002815; (1970); ; vol. 73; nb. 66258 View in Reaxys Baeckstroem; Sundstroem; Acta Chemica Scandinavica (1947-1973); vol. 24; (1970); p. 716 View in Reaxys Patent; HOFFMANN-LA ROCHE INC.; Nutley; N. Y.; US3919322; (1975); ; vol. 84; nb. 43460; (1975) View in Reaxys Patent; CIBA-GEIGY; FR2212317; (1974); DE2359410; ; vol. 81; nb. 91205; (1974) View in Reaxys Barker; Settine; Organic Preparations and Procedures International; vol. 11; (1979); p. 87,90 View in Reaxys Krishnamurty; Prasad; Tetrahedron Letters; (1975); p. 2511 View in Reaxys

O O

3-oxo-octanoic acid (1)-ethyl ester

O OH

Rx-ID: 6189902 View in Reaxys 11/70 Yield

Conditions & References With sodium, T= 140 - 150 °C , Erhitzen des Reaktionsprodukts mit KOH auf 250grad Asahina; Asano; Chemische Berichte; vol. 65; (1932); p. 475,581; Yakugaku Zasshi; vol. 52; (1932); p. 417,428 View in Reaxys

HO HO

O O

OH O

H 2N 2

olivetonide OH

Rx-ID: 7924432 View in Reaxys 12/70

5/26

2018-02-18 01:17:24

Yield

Conditions & References T= 150 °C , im Rohr Asahina; Asano; Chemische Berichte; vol. 65; (1932); p. 475,581; Yakugaku Zasshi; vol. 52; (1932); p. 417,428 View in Reaxys Zopf; Justus Liebigs Annalen der Chemie; vol. 313; (1900); p. 342; ; vol. 14; (1903); p. 1. Heft. S. 112 View in Reaxys

HO HO O

O O

OH H 2N 2

olivetonide OH

Rx-ID: 7924433 View in Reaxys 13/70 Yield

Conditions & References Asahina; Asano; Chemische Berichte; vol. 65; (1932); p. 475,581; Yakugaku Zasshi; vol. 52; (1932); p. 417,428 View in Reaxys Zopf; Justus Liebigs Annalen der Chemie; vol. 313; (1900); p. 342; ; vol. 14; (1903); p. 1. Heft. S. 112 View in Reaxys

Rx-ID: 17115413 View in Reaxys 14/70 Yield

Conditions & References Reaction Steps: 5 1: Et3N / tetrahydrofuran / 1 h / 0 - 20 °C 2: 41 percent / Li, naphthalene / tetrahydrofuran / 2 h / -30 - 0 °C 3: 96 percent / Et3N / tetrahydrofuran / 1.08 h / 0 °C 4: 95 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 5: 81 percent / 45percent HBr, glacial AcOH / 3 h / Heating With naphthalene, hydrogen bromide, lithium, acetic acid, triethylamine, sodium iodide, zinc in tetrahydrofuran, 1,2dimethoxyethane Alonso, Emma; Ramon, Diego J.; Yus, Miguel; Journal of Organic Chemistry; vol. 62; nb. 2; (1997); p. 417 - 421 View in Reaxys Reaction Steps: 3 1: PBr3 2: CuI 3: aq. HCl, Py With pyridine, hydrogenchloride, copper(l) iodide, phosphorus tribromide Petrzilka,T. et al.; Helvetica Chimica Acta; vol. 52; nb. 4; (1969); p. 1102 - 1134 View in Reaxys O OH

O O

Rx-ID: 17133050 View in Reaxys 15/70 Yield

Conditions & References Reaction Steps: 4 1: 41 percent / Li, naphthalene / tetrahydrofuran / 2 h / -30 - 0 °C 2: 96 percent / Et3N / tetrahydrofuran / 1.08 h / 0 °C

6/26

2018-02-18 01:17:24

3: 95 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 4: 81 percent / 45percent HBr, glacial AcOH / 3 h / Heating With naphthalene, hydrogen bromide, lithium, acetic acid, triethylamine, sodium iodide, zinc in tetrahydrofuran, 1,2dimethoxyethane Alonso, Emma; Ramon, Diego J.; Yus, Miguel; Journal of Organic Chemistry; vol. 62; nb. 2; (1997); p. 417 - 421 View in Reaxys

OH O

Rx-ID: 17133125 View in Reaxys 16/70 Yield

Conditions & References Reaction Steps: 3 1: 96 percent / Et3N / tetrahydrofuran / 1.08 h / 0 °C 2: 95 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 3: 81 percent / 45percent HBr, glacial AcOH / 3 h / Heating With hydrogen bromide, acetic acid, triethylamine, sodium iodide, zinc in tetrahydrofuran, 1,2-dimethoxyethane Alonso, Emma; Ramon, Diego J.; Yus, Miguel; Journal of Organic Chemistry; vol. 62; nb. 2; (1997); p. 417 - 421 View in Reaxys

O S

O O

Rx-ID: 17137054 View in Reaxys 17/70 Yield

Conditions & References Reaction Steps: 2 1: 95 percent / NaI, Zn / 1,2-dimethoxy-ethane / 8 h / Heating 2: 81 percent / 45percent HBr, glacial AcOH / 3 h / Heating With hydrogen bromide, acetic acid, sodium iodide, zinc in 1,2-dimethoxyethane Alonso, Emma; Ramon, Diego J.; Yus, Miguel; Journal of Organic Chemistry; vol. 62; nb. 2; (1997); p. 417 - 421 View in Reaxys

Rx-ID: 18309104 View in Reaxys 18/70 Yield

Conditions & References Reaction Steps: 3 1: 1.) Mg; MeI / diethyl ether / 1.) 3 h, reflux; 2.) 1 h, reflux 2: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 3: NaI, ClSiMe3 / acetonitrile / 36 h / Heating With chloro-trimethyl-silane, sulfuric acid, hydrogen, magnesium, sodium iodide, methyl iodide, palladium on activated charcoal in diethyl ether, ethyl acetate, acetonitrile Ayer, William A.; Browne, Lois M.; Lovell, Sarah H.; Phytochemistry (Elsevier); vol. 22; nb. 10; (1983); p. 2267 2272 View in Reaxys

7/26

2018-02-18 01:17:24

OH H

OH O

Rx-ID: 18310647 View in Reaxys 19/70 Yield

Conditions & References Reaction Steps: 2 1: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 2: NaI, ClSiMe3 / acetonitrile / 36 h / Heating With chloro-trimethyl-silane, sulfuric acid, hydrogen, sodium iodide, palladium on activated charcoal in ethyl acetate, acetonitrile Ayer, William A.; Browne, Lois M.; Lovell, Sarah H.; Phytochemistry (Elsevier); vol. 22; nb. 10; (1983); p. 2267 2272 View in Reaxys O

O HO O

Rx-ID: 18318648 View in Reaxys 20/70 Yield

Conditions & References Reaction Steps: 5 1: 89 percent / (COCl)2 / benzene / 2 h, room t., 1 h, reflux 2: 70 percent / NaOAc, H2 / 10percent Pd-C / 2427.2 Torr / 1h, then 60 degC, overnight 3: 1.) Mg; MeI / diethyl ether / 1.) 3 h, reflux; 2.) 1 h, reflux 4: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 5: NaI, ClSiMe3 / acetonitrile / 36 h / Heating With chloro-trimethyl-silane, oxalyl dichloride, sulfuric acid, hydrogen, sodium acetate, magnesium, sodium iodide, methyl iodide, palladium on activated charcoal in diethyl ether, ethyl acetate, acetonitrile, benzene Ayer, William A.; Browne, Lois M.; Lovell, Sarah H.; Phytochemistry (Elsevier); vol. 22; nb. 10; (1983); p. 2267 2272 View in Reaxys Reaction Steps: 7 4: 28.8 g / fluoroboric acid, sodium nitrite / H2O 5: 7.6 g / warming, distillation 6: 60 percent / lithium chips / 0.5 h 7: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys Reaction Steps: 4 1: LiAlH4 2: PBr3 3: CuI 4: aq. HCl, Py With pyridine, hydrogenchloride, copper(l) iodide, lithium aluminium tetrahydride, phosphorus tribromide Petrzilka,T. et al.; Helvetica Chimica Acta; vol. 52; nb. 4; (1969); p. 1102 - 1134 View in Reaxys

8/26

2018-02-18 01:17:24

O Cl O

Rx-ID: 18318668 View in Reaxys 21/70 Yield

Conditions & References Reaction Steps: 4 1: 70 percent / NaOAc, H2 / 10percent Pd-C / 2427.2 Torr / 1h, then 60 degC, overnight 2: 1.) Mg; MeI / diethyl ether / 1.) 3 h, reflux; 2.) 1 h, reflux 3: hydrogen, conc. H2SO4 / 10percent Pd-C / ethyl acetate / 4 h / 2942.03 Torr / Ambient temperature 4: NaI, ClSiMe3 / acetonitrile / 36 h / Heating With chloro-trimethyl-silane, sulfuric acid, hydrogen, sodium acetate, magnesium, sodium iodide, methyl iodide, palladium on activated charcoal in diethyl ether, ethyl acetate, acetonitrile Ayer, William A.; Browne, Lois M.; Lovell, Sarah H.; Phytochemistry (Elsevier); vol. 22; nb. 10; (1983); p. 2267 2272 View in Reaxys Reaction Steps: 6 3: 28.8 g / fluoroboric acid, sodium nitrite / H2O 4: 7.6 g / warming, distillation 5: 60 percent / lithium chips / 0.5 h 6: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys

Rx-ID: 19192489 View in Reaxys 22/70 Yield

Conditions & References Reaction Steps: 3 1: 92 percent / diethyl ether / 2 h / Ambient temperature 2: p-toluenesulfonic acid / benzene / Heating 3: H2 / 10percent Pd/C / ethanol With hydrogen, toluene-4-sulfonic acid, palladium on activated charcoal in diethyl ether, ethanol, benzene Anand; Ranjan; Bulletin of the Chemical Society of Japan; vol. 56; nb. 6; (1983); p. 1889 - 1890 View in Reaxys OH

O HO OH

Rx-ID: 19194087 View in Reaxys 23/70 Yield

Conditions & References Reaction Steps: 6 1: 97 percent / K2CO3 / dimethylformamide / 12 h / Heating 2: 95 percent / LiAlH4 / diethyl ether 3: 93 percent / pyridinium chlorochromate, CH3COONa / CH2Cl2 / 1 h 4: 92 percent / diethyl ether / 2 h / Ambient temperature 5: p-toluenesulfonic acid / benzene / Heating 6: H2 / 10percent Pd/C / ethanol

9/26

2018-02-18 01:17:24

With lithium aluminium tetrahydride, hydrogen, sodium acetate, potassium carbonate, toluene-4-sulfonic acid, pyridinium chlorochromate, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, N,N-dimethyl-formamide, benzene Anand; Ranjan; Bulletin of the Chemical Society of Japan; vol. 56; nb. 6; (1983); p. 1889 - 1890 View in Reaxys Reaction Steps: 8 1: 84 percent / sodium hydroxide / heating 5: 28.8 g / fluoroboric acid, sodium nitrite / H2O 6: 7.6 g / warming, distillation 7: 60 percent / lithium chips / 0.5 h 8: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With sodium hydroxide, tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys

Rx-ID: 19194733 View in Reaxys 24/70 Yield

Conditions & References Reaction Steps: 4 1: 93 percent / pyridinium chlorochromate, CH3COONa / CH2Cl2 / 1 h 2: 92 percent / diethyl ether / 2 h / Ambient temperature 3: p-toluenesulfonic acid / benzene / Heating 4: H2 / 10percent Pd/C / ethanol With hydrogen, sodium acetate, toluene-4-sulfonic acid, pyridinium chlorochromate, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, benzene Anand; Ranjan; Bulletin of the Chemical Society of Japan; vol. 56; nb. 6; (1983); p. 1889 - 1890 View in Reaxys

O O

O OH

Rx-ID: 19196744 View in Reaxys 25/70 Yield

Conditions & References Reaction Steps: 5 1: 95 percent / LiAlH4 / diethyl ether 2: 93 percent / pyridinium chlorochromate, CH3COONa / CH2Cl2 / 1 h 3: 92 percent / diethyl ether / 2 h / Ambient temperature 4: p-toluenesulfonic acid / benzene / Heating 5: H2 / 10percent Pd/C / ethanol With lithium aluminium tetrahydride, hydrogen, sodium acetate, toluene-4-sulfonic acid, pyridinium chlorochromate, palladium on activated charcoal in diethyl ether, ethanol, dichloromethane, benzene Anand; Ranjan; Bulletin of the Chemical Society of Japan; vol. 56; nb. 6; (1983); p. 1889 - 1890

10/26

2018-02-18 01:17:24

View in Reaxys

OH O OH

O OH

Rx-ID: 19214813 View in Reaxys 26/70 Yield

Conditions & References Reaction Steps: 2 1: p-toluenesulfonic acid / benzene / Heating 2: H2 / 10percent Pd/C / ethanol With hydrogen, toluene-4-sulfonic acid, palladium on activated charcoal in ethanol, benzene Anand; Ranjan; Bulletin of the Chemical Society of Japan; vol. 56; nb. 6; (1983); p. 1889 - 1890 View in Reaxys

(+-)-6,6,9-trimethyl-7,8,9,10-tetrahydro-6Hbenzo<c>chromene-1,3-diol

Rx-ID: 20588066 View in Reaxys 27/70 Yield

Conditions & References Reaction Steps: 2 1: 60 percent / lithium chips / 0.5 h 2: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With pyridine hydrochloride, boron tribromide, lithium in dichloromethane Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys O

O O O

Rx-ID: 20591251 View in Reaxys 28/70 Yield

Conditions & References Reaction Steps: 11 1: 78 percent / hydrazine hydrate / 2 h / Heating 2: 63 percent / sodium nitrite, hydrochloric acid (2M), acetic acid (glacial) / H2O / 1 h / -10 °C 3: 93 percent / toluene / 2.5 h / Heating 4: 8.7 g / sodium hydroxide (20percent) / 60 °C 8: 28.8 g / fluoroboric acid, sodium nitrite / H2O 9: 7.6 g / warming, distillation 10: 60 percent / lithium chips / 0.5 h 11: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With hydrogenchloride, sodium hydroxide, tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, hydrazine hydrate, acetic acid, sodium nitrite in dichloromethane, water, toluene Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys

11/26

2018-02-18 01:17:24

H 2N O O

Rx-ID: 20593284 View in Reaxys 29/70 Yield

Conditions & References Reaction Steps: 5 2: 28.8 g / fluoroboric acid, sodium nitrite / H2O 3: 7.6 g / warming, distillation 4: 60 percent / lithium chips / 0.5 h 5: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys O

O N

N O

Rx-ID: 20594693 View in Reaxys 30/70 Yield

Conditions & References Reaction Steps: 9 1: 93 percent / toluene / 2.5 h / Heating 2: 8.7 g / sodium hydroxide (20percent) / 60 °C 6: 28.8 g / fluoroboric acid, sodium nitrite / H2O 7: 7.6 g / warming, distillation 8: 60 percent / lithium chips / 0.5 h 9: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With sodium hydroxide, tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water, toluene Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys O

O H 2N

NH O

Rx-ID: 20596338 View in Reaxys 31/70 Yield

Conditions & References Reaction Steps: 10 1: 63 percent / sodium nitrite, hydrochloric acid (2M), acetic acid (glacial) / H2O / 1 h / -10 °C 2: 93 percent / toluene / 2.5 h / Heating 3: 8.7 g / sodium hydroxide (20percent) / 60 °C 7: 28.8 g / fluoroboric acid, sodium nitrite / H2O 8: 7.6 g / warming, distillation 9: 60 percent / lithium chips / 0.5 h 10: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With hydrogenchloride, sodium hydroxide, tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, acetic acid, sodium nitrite in dichloromethane, water, toluene Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys

12/26

2018-02-18 01:17:24

Rx-ID: 20596611 View in Reaxys 32/70 Yield

F (v4)

B FF

N+ N OH

Rx-ID: 20598278 View in Reaxys 33/70 Yield

Conditions & References Reaction Steps: 3 1: 7.6 g / warming, distillation 2: 60 percent / lithium chips / 0.5 h 3: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With pyridine hydrochloride, boron tribromide, lithium in dichloromethane Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys

NH 2

Rx-ID: 20620918 View in Reaxys 34/70 Yield

Conditions & References Reaction Steps: 4 1: 28.8 g / fluoroboric acid, sodium nitrite / H2O 2: 7.6 g / warming, distillation 3: 60 percent / lithium chips / 0.5 h 4: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys O

N O O

Rx-ID: 20621547 View in Reaxys 35/70 Yield

Conditions & References Reaction Steps: 8 1: 8.7 g / sodium hydroxide (20percent) / 60 °C

13/26

2018-02-18 01:17:24

5: 28.8 g / fluoroboric acid, sodium nitrite / H2O 6: 7.6 g / warming, distillation 7: 60 percent / lithium chips / 0.5 h 8: boron tribromide, pyridine hydrochloride / CH2Cl2 / 24 h / -78 °C With sodium hydroxide, tetrafluoroboric acid, pyridine hydrochloride, boron tribromide, lithium, sodium nitrite in dichloromethane, water Durrani, Aziz A.; Tyman, John H. P.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 1658 - 1666 View in Reaxys OH Br

Br OH

OH O

Rx-ID: 22224462 View in Reaxys 36/70 Yield

Conditions & References Reaction Steps: 2 1: palladium; aq. NaOH solution / Hydrogenation 2: aqueous NaOH With sodium hydroxide, palladium Anker; Cook; Journal of the Chemical Society; (1945); p. 311 View in Reaxys Reaction Steps: 2 1: H2 / Pd-C 2: aq. NaOH With sodium hydroxide, hydrogen, palladium on activated charcoal Korte,F.; Sieper,H.; Justus Liebigs Annalen der Chemie; vol. 630; (1960); p. 71 - 83 View in Reaxys

Rx-ID: 22784067 View in Reaxys 37/70 Yield

Conditions & References Reaction Steps: 2 1: CuI 2: aq. HCl, Py With pyridine, hydrogenchloride, copper(l) iodide Petrzilka,T. et al.; Helvetica Chimica Acta; vol. 52; nb. 4; (1969); p. 1102 - 1134 View in Reaxys O HO

O O

Rx-ID: 25270121 View in Reaxys 38/70 Yield

Conditions & References 2 : EXAMPLE 2 EXAMPLE 2

14/26

2018-02-18 01:17:24

1.0 g (0.00338 mole) of 2,4-dihydroxy-6-pentylisophthalic acid dimethyl ester is stirred in 10 ml of a mixture of conc. sulphuric acid and water (volume ratio = 5:1) until a solution is obtained, and this then heated for 4 hours in a bath at 100°. After cooling, the solution is poured on ice and extracted twice with ether (100 ml each time). The combined ethereal layers are extracted with 2 portions of 1N sodium hydroxide solution and the basic extracts acidified with hydrochloric acid; the reaction product precipitating in the form of oil is subsequently taken up in ether. The solution dried with magnesium sulphate yields, after concentration in vacuo, 481 mg of yellowish oil, which crystallises on standing. The yield of crude olivetol amounts to 79percent of theory. With conc. sulphuric acid in water Patent; Ciba-Geigy Corporation; US4020098; (1977); (A1) English View in Reaxys O OH OH O

Rx-ID: 38513612 View in Reaxys 39/70 Yield 69.3 %

Conditions & References B.2 : 2. l-N-Pentyl-3, 5-dihydroxybenzene ( Olivetol). [0120] To a stirring ice-cooled solution of methyl 6-N-pentyl-2-hydroxy-4-oxo-cyclohex-2- ene-l-carboxylate (58.4 g, 0.24 mol) dissolved in 115 mL dimethylformamide was added dropwise 37.9 g (0.23 mol) of bromine dissolved in 60 mL of dimethylformamide. At the end of the addition (ca. 90 min) the reaction mixture was slowly heated to 80° C during which time the evolution of carbon dioxide became quite vigorous. [0121] The reaction was maintained at this temperature until gas evolution had ceased following which the reaction was further heated to 160° C and held at this temperature for approximately 10 hours. After heating, the reaction was allowed to cool and the solvent DMF was removed under reduced pressure. The residue thus obtained was treated with water (80 mL) and extracted twice with 250 mL of ether. The combined ether layers were washed with water, then washed with 2 X 80 mL of a 10percent solution of sodium bisulfite, 2 X 80 mL of a 10percent solution of acetic acid, and then again with water. [0122] After drying over anhydrous sodium sulfate the solvent was removed under reduced pressure to give 46.8 g of a viscous oil. The oil was distilled under reduced pressure to give 30.3 g (0.168 mol) (69.3percento) of olivetol as product. HPLC analysis indicated 97.5percent purity. With bromine in N,N-dimethyl-formamide, Time= 10h, T= 160 °C , Cooling with ice Patent; FULL SPECTRUM LABORATORIES LIMITED; WINNICKI, Robert; DONSKY, Marc; WO2014/134281; (2014); (A1) English View in Reaxys

69.3 %

B.2 : 2. 1-N-Pentyl-3,5-dihydroxybenzene To a stirring ice-cooled solution of methyl 6-N-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l- carboxylate (58.4 g, 0.24 mol) dissolved in 115 mL dimethylformamide was added dropwise 37.9 g (0.23 mol) of bromine dissolved in 60 mL of dimethylformamide. At the end of the addition (ca. 90 min) the reaction mixture was slowly heated to 80° C during which time the evolution of carbon dioxide became quite vigorous. The reaction was maintained at this temperature until gas evolution had ceased following which the reaction was further heated to 160° C and held at this temperature for approximately 10 hours. After heating, the reaction was allowed to cool and the solvent DMF was removed under reduced pressure. The residue thus obtained was treated with water (80 mL) and extracted twice with 250 mL of ether. The combined ether layers were washed with water, then washed with 2 X 80 mL of a 10percent solution of sodium bisulfite, 2 X 80 mL of a 10percent solution of acetic acid, and then again with water. After drying over anhydrous sodium sulfate the solvent was removed under reduced pressure to give 46.8 g of a viscous oil. The oil was distilled under reduced pressure to give 30.3 g (0.168 mol) (69.3percent) of olivetol as product. HPLC analysis indicated 97.5percent purity. With bromine in N,N-dimethyl-formamide, T= 80 - 160 °C Patent; FULL SPECTRUM LABORATORIES LIMITED; DONSKY, Marc; SUN, Mingyang; PEET, Richard; WINNICKI, Robert; (107 pag.); WO2016/30828; (2016); (A1) English View in Reaxys

15/26

2018-02-18 01:17:24

69.3 %

1.B : B. 1-n-Pentyl-3,5-dihydroxybenzene (Olivetol) B. 1-n-Pentyl-3,5-dihydroxybenzene (Olivetol) (0126) (0127) To a stirring ice-cooled solution of methyl 6-N-pentyl-2hydroxy-4-oxo-cyclohex-2-ene-1-carboxylate (58.4 g, 0.24 mol) dissolved in 115 mL dimethylformamide was added dropwise 37.9 g (0.23 mol) of bromine dissolved in 60 mL of dimethylformamide. At the end of the addition (ca. 90 min) the reaction mixture was slowly heated to 80° C. during which time the evolution of carbon dioxide became quite vigorous. (0128) The reaction was maintained at this temperature until gas evolution had ceased following which the reaction was further heated to 160° C. and held at this temperature for approximately 10 hours. After heating, the reaction was allowed to cool and the solvent DMF was removed under reduced pressure. The residue thus obtained was treated with water (80 mL) and extracted twice with 250 mL of ether. The combined ether layers were washed with water, then washed with 2×80 mL of a 10percent solution of sodium bisulfite, 2×80 mL of a 10percent solution of acetic acid, and then again with water. (0129) After drying over anhydrous sodium sulfate the solvent was removed under reduced pressure to give 46.8 g of viscous oil. The oil was distilled under reduced pressure to give 30.3 g (0.168 mol) (69.3percent) of olivetol as product. HPLC analysis indicated 97.5percent purity. With bromine in N,N-dimethyl-formamide, Time= 11.5h, T= 160 °C , Cooling with ice Patent; Full Spectrum Laboratories Ltd; Kavarana, Malcolm J.; Peet, Richard C.; (23 pag.); US2017/283837; (2017); (A1) English View in Reaxys

69.3 %

A.ii : ii. 1-n-Pentyl-3,5-dihydroxybenzene (Olivetol) To a stirring ice-cooled solution of methyl 6—N-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-1-carboxylate (58.4 g, 0.24 mol) dissolved in 115 mL dimethylformamide was added dropwise 37.9 g (0.23 mol) of bromine dissolved in 60 mL of dimethylformamide. At the end of the addition (ca. 90 min) the reaction mixture was slowly heated to 80° C. during which time the evolution of carbon dioxide became quite vigorous. The reaction was maintained at this temperature until gas evolution had ceased following which the reaction was further heated to 160° C. and held at this temperature for approximately 10 hours. After heating, the reaction was allowed to cool and the solvent DMF was removed under reduced pressure. The residue thus obtained was treated with water (80 mL) and extracted twice with 250 mL of ether. The combined ether layers were washed with water, then washed with 2×80 mL of a 10percent solution of sodium bisulfite, 2×80 mL of a 10percent solution of acetic acid, and then again with water After drying over anhydrous sodium sulfate the solvent was removed under reduced pressure to give 46.8 g of viscous oil. The oil was distilled under reduced pressure to give 30.3g (0.168 mol) (69.3percent) of olivetol as product. HPLC analysis indicated 97.5percent purity. With bromine in N,N-dimethyl-formamide, Time= 10h, T= 160 °C , Cooling with ice Patent; Full Spectrum Laboratories Ltd; Peet, Richard C.; Kavarana, Malcolm J.; (26 pag.); US2017/298399; (2017); (A1) English View in Reaxys

69.3 %

I.ii : ii. 1-n-Penyl-3,5-dihydroxybenzene (Olivetol) [0134] To a stirring ice-cooled solution of methyl 6-N-pentyl-2-hydroxy-4-oxo-cyclohex-2-ene-l-carboxylate (58.4 g, 0.24 mol) dissolved in 115 mL dimethylformamide was added dropwise 37.9 g (0.23 mol) of bromine dissolved in 60 mL of dimethylformamide. At the end of the addition (ca. 90 min) the reaction mixture was slowly heated to 80° C. during which time the evolution of carbon dioxide became quite vigorous. [0135] The reaction was maintained at this temperature until gas evolution had ceased following which the reaction was further heated to 160° C. and held at this temperature for approximately 10 hours. After heating, the reaction was allowed to cool and the solvent DMF was removed under reduced pressure. The residue thus obtained was treated with water (80 mL) and extracted twice with 250 mL of ether. The combined ether layers were washed with water, then washed with 2*80 mL of a 10percent solution of sodium bisultite, 2*80 mL of a 10percent solution of acetic acid, and then again with water. [0136] After drying over anhydrous sodium sulfate the solvent was removed under reduced pressure to give 46.8 g of viscous oil. The oil was distilled under reduced pressure to give 30.3 g (0.168 mol) (69.3percent) of olivetol as product. HPLC analysis indicated 97.5percent purity. With bromine in N,N-dimethyl-formamide, Time= 11.5h, T= 80 - 160 °C , Cooling with ice Patent; Full Spectrum Laboratories Ltd; Peet, Richard C.; Kavarana, Malcolm J.; (25 pag.); US2017/362195; (2017); (A1) English View in Reaxys

16/26

2018-02-18 01:17:24

Rx-ID: 45909143 View in Reaxys 40/70 Yield

Conditions & References Reaction Steps: 2 1: potassium phosphate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / toluene / 16 h / 110 °C / Inert atmosphere; Enzymatic reaction 2: boron tribromide / dichloromethane / 1.5 h / -15 - 20 °C / Inert atmosphere With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride, potassium phosphate, boron tribromide in dichloromethane, toluene, 1: |Suzuki Coupling Sisa, Miroslav; Dvorakova, Marcela; Vanek, Tomas; Tetrahedron; vol. 73; nb. 35; (2017); p. 5297 - 5301 View in Reaxys Reaction Steps: 3 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / dichloromethane / 20 - 65 °C / Inert atmosphere 2: palladium 10 on activated carbon; hydrogen / methanol / 20 °C / 3750.38 Torr 3: boron tribromide / dichloromethane / 1.5 h / -15 - 20 °C / Inert atmosphere With bis-triphenylphosphine-palladium(II) chloride, copper(l) iodide, palladium 10 on activated carbon, hydrogen, boron tribromide, triethylamine in methanol, dichloromethane, 1: |Sonogashira Cross-Coupling Sisa, Miroslav; Dvorakova, Marcela; Vanek, Tomas; Tetrahedron; vol. 73; nb. 35; (2017); p. 5297 - 5301 View in Reaxys

Rx-ID: 45909156 View in Reaxys 41/70 Yield

Conditions & References Reaction Steps: 3 1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / dichloromethane / 20 - 65 °C / Inert atmosphere 2: palladium 10 on activated carbon; hydrogen / methanol / 20 °C / 3750.38 Torr 3: boron tribromide / dichloromethane / 1.5 h / -15 - 20 °C / Inert atmosphere With bis-triphenylphosphine-palladium(II) chloride, copper(l) iodide, palladium 10 on activated carbon, hydrogen, boron tribromide, triethylamine in methanol, dichloromethane, 1: |Sonogashira Cross-Coupling Sisa, Miroslav; Dvorakova, Marcela; Vanek, Tomas; Tetrahedron; vol. 73; nb. 35; (2017); p. 5297 - 5301 View in Reaxys

OH HO

B OH

Rx-ID: 45909162 View in Reaxys 42/70 Yield

17/26

2018-02-18 01:17:24

O OH

Rx-ID: 45909178 View in Reaxys 43/70 Yield

Conditions & References Reaction Steps: 2 1: palladium 10 on activated carbon; hydrogen / methanol / 20 °C / 3750.38 Torr 2: boron tribromide / dichloromethane / 1.5 h / -15 - 20 °C / Inert atmosphere With palladium 10 on activated carbon, hydrogen, boron tribromide in methanol, dichloromethane Sisa, Miroslav; Dvorakova, Marcela; Vanek, Tomas; Tetrahedron; vol. 73; nb. 35; (2017); p. 5297 - 5301 View in Reaxys

O 2H

H OH

Rx-ID: 2048224 View in Reaxys 44/70 Yield

Conditions & References

97 %

With boron tribromide in dichloromethane, T= -78 - 20 °C Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys

75 %

With trimethylsilyl iodide in chloroform, Time= 48h, T= 40 °C Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys With boron tribromide in dichloromethane Pitt; Hobbs; Schran; et al.; Journal of Labelled Compounds; vol. 11; nb. 4; (1975); p. 551 - 575 View in Reaxys

H OH

Rx-ID: 14440773 View in Reaxys 45/70 Yield

Conditions & References Reaction Steps: 4 1.1: magnesium turnings / diethyl ether 1.2: 88 percent / CeCl3 / tetrahydrofuran; diethyl ether / 1.5 h / -78 - 20 °C 2.1: triethylamine / tetrahydrofuran / 0.33 h 3.1: 11.92 g / lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C 4.1: 97 percent / BBr3 / CH2Cl2 / -78 - 20 °C With boron tribromide, lithium triethylborohydride, magnesium, triethylamine in tetrahydrofuran, diethyl ether, dichloromethane, 1.2: Grignard reaction Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys

18/26

2018-02-18 01:17:24

O 2H

Rx-ID: 14451231 View in Reaxys 46/70 Yield

Conditions & References Reaction Steps: 3 1: triethylamine / tetrahydrofuran / 0.33 h 2: 11.92 g / lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C 3: 97 percent / BBr3 / CH2Cl2 / -78 - 20 °C With boron tribromide, lithium triethylborohydride, triethylamine in tetrahydrofuran, dichloromethane Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys

H OH

O S

O OH

Rx-ID: 14453617 View in Reaxys 47/70 Yield

Conditions & References Reaction Steps: 2 1: 11.92 g / lithium triethylborohydride / tetrahydrofuran / 0 - 20 °C 2: 97 percent / BBr3 / CH2Cl2 / -78 - 20 °C With boron tribromide, lithium triethylborohydride in tetrahydrofuran, dichloromethane Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys

H OH

Rx-ID: 20091330 View in Reaxys 48/70 Yield

Conditions & References Reaction Steps: 6 1: phosphorous tribromide / CH2Cl2 / 1 h / Ambient temperature 2: 80 percent / diethyl ether / 30 h / Ambient temperature 3: 1.) borane-dimethyl sulfide complex; 2.) 3N NaOH, 30percent aqueous hydrogen peroxide / 1.) dichloromethane, 0 deg C, 25 min, then r.t., 3 h; 2.) dichloromethane, ethanol, reflux, 1 h 4: 70 percent / trimethylsilyl chloride, lithium bromide / acetonitrile / 12 h / Heating 5: 60 percent / dilithium tetrachlorocuprate / tetrahydrofuran; diethyl ether / 16 h / Ambient temperature 6: 75 percent / trimethylsilyl iodide / CHCl3 / 48 h / 40 °C With sodium hydroxide, chloro-trimethyl-silane, trimethylsilyl iodide, dimethylsulfide borane complex, dihydrogen peroxide, phosphorus tribromide, lithium bromide, dilithium tetrachlorocuprate in tetrahydrofuran, diethyl ether, dichloromethane, chloroform, acetonitrile Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys

19/26

2018-02-18 01:17:24

Rx-ID: 20092978 View in Reaxys 49/70 Yield

Conditions & References Reaction Steps: 5 1: 80 percent / diethyl ether / 30 h / Ambient temperature 2: 1.) borane-dimethyl sulfide complex; 2.) 3N NaOH, 30percent aqueous hydrogen peroxide / 1.) dichloromethane, 0 deg C, 25 min, then r.t., 3 h; 2.) dichloromethane, ethanol, reflux, 1 h 3: 70 percent / trimethylsilyl chloride, lithium bromide / acetonitrile / 12 h / Heating 4: 60 percent / dilithium tetrachlorocuprate / tetrahydrofuran; diethyl ether / 16 h / Ambient temperature 5: 75 percent / trimethylsilyl iodide / CHCl3 / 48 h / 40 °C With sodium hydroxide, chloro-trimethyl-silane, trimethylsilyl iodide, dimethylsulfide borane complex, dihydrogen peroxide, lithium bromide, dilithium tetrachlorocuprate in tetrahydrofuran, diethyl ether, chloroform, acetonitrile Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys

H OH

Rx-ID: 20094618 View in Reaxys 50/70 Yield

Conditions & References Reaction Steps: 3 1: 70 percent / trimethylsilyl chloride, lithium bromide / acetonitrile / 12 h / Heating 2: 60 percent / dilithium tetrachlorocuprate / tetrahydrofuran; diethyl ether / 16 h / Ambient temperature 3: 75 percent / trimethylsilyl iodide / CHCl3 / 48 h / 40 °C With chloro-trimethyl-silane, trimethylsilyl iodide, lithium bromide, dilithium tetrachlorocuprate in tetrahydrofuran, diethyl ether, chloroform, acetonitrile Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys

O O

H OH

HO O

Rx-ID: 20101089 View in Reaxys 51/70 Yield

Conditions & References Reaction Steps: 7 1: lithium aluminum hydride / diethyl ether / 16 h / Ambient temperature 2: phosphorous tribromide / CH2Cl2 / 1 h / Ambient temperature 3: 80 percent / diethyl ether / 30 h / Ambient temperature 4: 1.) borane-dimethyl sulfide complex; 2.) 3N NaOH, 30percent aqueous hydrogen peroxide / 1.) dichloromethane, 0 deg C, 25 min, then r.t., 3 h; 2.) dichloromethane, ethanol, reflux, 1 h 5: 70 percent / trimethylsilyl chloride, lithium bromide / acetonitrile / 12 h / Heating 6: 60 percent / dilithium tetrachlorocuprate / tetrahydrofuran; diethyl ether / 16 h / Ambient temperature 7: 75 percent / trimethylsilyl iodide / CHCl3 / 48 h / 40 °C With sodium hydroxide, lithium aluminium tetrahydride, chloro-trimethyl-silane, trimethylsilyl iodide, dimethylsulfide borane complex, dihydrogen peroxide, phosphorus tribromide, lithium bromide, dilithium tetrachlorocuprate in tetrahydrofuran, diethyl ether, dichloromethane, chloroform, acetonitrile Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys

20/26

2018-02-18 01:17:24

Rx-ID: 20103032 View in Reaxys 52/70 Yield

Conditions & References Reaction Steps: 4 1: 1.) borane-dimethyl sulfide complex; 2.) 3N NaOH, 30percent aqueous hydrogen peroxide / 1.) dichloromethane, 0 deg C, 25 min, then r.t., 3 h; 2.) dichloromethane, ethanol, reflux, 1 h 2: 70 percent / trimethylsilyl chloride, lithium bromide / acetonitrile / 12 h / Heating 3: 60 percent / dilithium tetrachlorocuprate / tetrahydrofuran; diethyl ether / 16 h / Ambient temperature 4: 75 percent / trimethylsilyl iodide / CHCl3 / 48 h / 40 °C With sodium hydroxide, chloro-trimethyl-silane, trimethylsilyl iodide, dimethylsulfide borane complex, dihydrogen peroxide, lithium bromide, dilithium tetrachlorocuprate in tetrahydrofuran, diethyl ether, chloroform, acetonitrile Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys

Rx-ID: 20103191 View in Reaxys 53/70 Yield

Conditions & References Reaction Steps: 2 1: 60 percent / dilithium tetrachlorocuprate / tetrahydrofuran; diethyl ether / 16 h / Ambient temperature 2: 75 percent / trimethylsilyl iodide / CHCl3 / 48 h / 40 °C With trimethylsilyl iodide, dilithium tetrachlorocuprate in tetrahydrofuran, diethyl ether, chloroform Girard, Michel; Moir, David B.; Apsimon, John W.; Canadian Journal of Chemistry; vol. 65; (1987); p. 189 - 190 View in Reaxys

O HO

H OH

Rx-ID: 22521799 View in Reaxys 54/70 Yield

Conditions & References Reaction Steps: 3 1: PBr3 / benzene 2: LiAlD4 / tetrahydrofuran / Heating 3: BBr3 / CH2Cl2 With lithium aluminium deuteride, boron tribromide, phosphorus tribromide in tetrahydrofuran, dichloromethane, benzene Pitt; Hobbs; Schran; et al.; Journal of Labelled Compounds; vol. 11; nb. 4; (1975); p. 551 - 575 View in Reaxys

O Br

Rx-ID: 22521807 View in Reaxys 55/70 Yield

Conditions & References Reaction Steps: 2 1: LiAlD4 / tetrahydrofuran / Heating

21/26

2018-02-18 01:17:24

2: BBr3 / CH2Cl2 With lithium aluminium deuteride, boron tribromide in tetrahydrofuran, dichloromethane Pitt; Hobbs; Schran; et al.; Journal of Labelled Compounds; vol. 11; nb. 4; (1975); p. 551 - 575 View in Reaxys O

Rx-ID: 22531197 View in Reaxys 56/70 Yield

Conditions & References Reaction Steps: 4 1: LiAlD4 / diethyl ether 2: PBr3 / benzene 3: LiAlD4 / tetrahydrofuran / Heating 4: BBr3 / CH2Cl2 With lithium aluminium deuteride, boron tribromide, phosphorus tribromide in tetrahydrofuran, diethyl ether, dichloromethane, benzene Pitt; Hobbs; Schran; et al.; Journal of Labelled Compounds; vol. 11; nb. 4; (1975); p. 551 - 575 View in Reaxys O

H OH

Rx-ID: 22532968 View in Reaxys 57/70 Yield

Conditions & References Reaction Steps: 5 1: H2 / Pd-C / ethanol 2: LiAlD4 / diethyl ether 3: PBr3 / benzene 4: LiAlD4 / tetrahydrofuran / Heating 5: BBr3 / CH2Cl2 With lithium aluminium deuteride, hydrogen, boron tribromide, phosphorus tribromide, palladium on activated charcoal in tetrahydrofuran, diethyl ether, ethanol, dichloromethane, benzene Pitt; Hobbs; Schran; et al.; Journal of Labelled Compounds; vol. 11; nb. 4; (1975); p. 551 - 575 View in Reaxys H

14C

H 14C OH

Rx-ID: 7198150 View in Reaxys 58/70 Yield

Conditions & References analog. mark. Dihydroolivetol (II), Quecksilberacetat. Liebman et al.; Journal of Labelled Compounds; vol. 7; (1971); p. 241,243 View in Reaxys

22/26

2018-02-18 01:17:24

OH H

Rx-ID: 7600953 View in Reaxys 59/70 Yield

Conditions & References 3H-Dimethylolivetol,

BBr3

Gill; Jones; Journal of Labelled Compounds; vol. 8; (1972); p. 237,241 View in Reaxys 2H

2H 2

Rx-ID: 9276410 View in Reaxys 60/70 Yield

Conditions & References

96 %

With boron tribromide in dichloromethane, Time= 4.75h, T= -78 - 20 °C Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys 2

H OH

2H 2H

Rx-ID: 14440777 View in Reaxys 61/70 Yield

Conditions & References Reaction Steps: 4 1.1: magnesium turnings / diethyl ether 1.2: 87 percent / CeCl3 / tetrahydrofuran; diethyl ether / 1.5 h / -78 - 20 °C 2.1: triethylamine / tetrahydrofuran / 0.33 h 3.1: 36.7 g / lithium triethylborohydride / tetrahydrofuran / 2.5 h / 0 - 20 °C 4.1: 96 percent / BBr3 / CH2Cl2 / 4.75 h / -78 - 20 °C With boron tribromide, lithium triethylborohydride, magnesium, triethylamine in tetrahydrofuran, diethyl ether, dichloromethane, 1.2: Grignard reaction Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys

O 2H

OH 2H

2H OH

2H 2H

O OH

Rx-ID: 14452511 View in Reaxys 62/70 Yield

Conditions & References Reaction Steps: 3 1: triethylamine / tetrahydrofuran / 0.33 h 2: 36.7 g / lithium triethylborohydride / tetrahydrofuran / 2.5 h / 0 - 20 °C 3: 96 percent / BBr3 / CH2Cl2 / 4.75 h / -78 - 20 °C With boron tribromide, lithium triethylborohydride, triethylamine in tetrahydrofuran, dichloromethane Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076

23/26

2018-02-18 01:17:24

View in Reaxys O

O S 2H

Rx-ID: 14454297 View in Reaxys 63/70 Yield

Conditions & References Reaction Steps: 2 1: 36.7 g / lithium triethylborohydride / tetrahydrofuran / 2.5 h / 0 - 20 °C 2: 96 percent / BBr3 / CH2Cl2 / 4.75 h / -78 - 20 °C With boron tribromide, lithium triethylborohydride in tetrahydrofuran, dichloromethane Nikas, Spyros P.; Thakur, Ganesh A.; Makriyannis, Alexandros; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 45; nb. 12; (2002); p. 1065 - 1076 View in Reaxys

aqueous KOH-solution

O HO

OH OH

Rx-ID: 7920432 View in Reaxys 64/70 Yield

Conditions & References Asahina; Fujikawa; Chemische Berichte; vol. 68; (1935); p. 634,636, 638 View in Reaxys

HO HO

OH HO

O O

O HO

Rx-ID: 54990 View in Reaxys 65/70 Yield

Conditions & References T= 150 - 200 °C Asahina; Asano; Chemische Berichte; vol. 65; (1932); p. 475,581; Yakugaku Zasshi; vol. 52; (1932); p. 417,428 View in Reaxys

24/26

2018-02-18 01:17:24

HO HO O

Rx-ID: 100151 View in Reaxys 66/70 Yield

Conditions & References Asahina; Asano; Chemische Berichte; vol. 65; (1932); p. 475,581; Yakugaku Zasshi; vol. 52; (1932); p. 417,428 View in Reaxys O

O S

OH O

S OH

racemate

Rx-ID: 1937272 View in Reaxys 67/70 Yield

Conditions & References With magnesium methanolate in methanol, 1.) 1 h, 2.) room temperature, 2 d, Yield given. Yields of byproduct given Jaxa-Chamiec, Albert A.; Sammes, Peter G.; Kennewell, Peter D.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1980); p. 170 - 175 View in Reaxys OH OH

Rx-ID: 31510089 View in Reaxys 68/70 Yield

Conditions & References 5 : Polyketide Synthase Enzyme Assays Spectral data obtained for all identified alkylresorcinolic products are provided in Table 1. Further confirmation for the formation of olivetol (AR5:0) and pentadecylresorcinol (AR15:0) in assays provided with hexanoly- and palmitoly-CoA starters was obtained by comparison of product retention times and mass spectra relative to authentic standards. GC-EI-MS: AR5:0-Rt 5.40 min, m/z 324 [M]+, m/z 309 [M-CH3]+, m/z 295 [5-propyl-1,3phenylene)bis(oxy)bis(TMS)]+, m/z 281 [(5-ethyl-1,3-phenylene)bis(oxy)bis(TMS)]+, m/z 268 [(5-methyl-1,3-phenylene)bis(oxy)bis(TMS)]+; AR15:0-Rt 10.17 min, m/z 464 [M]+, m/z 449 [M-CH3]+, m/z 361 [449+-2(CH2)]+, m/z 361 [449+-OTMS, +H]+, m/z 323 [5-pentyl-1,3-phenylene)bis(oxy)bis(TMS)+H]+, m/z 310 [5-butyl-1,3-phenylene)bis(oxy)bis(TMS)]+, m/z 310 [5-propyl-1,3-phenylene)bis(oxy)bis(TMS)]+, m/z 281 [5-ethyl-1,3-phenylene)bis(oxy)bis(TMS)]+, m/z 268 [5-methyl-1,3-phenylene)bis(oxy)bis(TMS)]+, m/z 253 [268+-CH3]+. Patent; Baerson, Scott R.; Pan, Zhiqiang; Rimando, Agnes M.; Dayan, Franck E.; Cook, Daniel; US2011/225676; (2011); (A1) English View in Reaxys

25/26

2018-02-18 01:17:24

Br OH

OH OH

Rx-ID: 2039627 View in Reaxys 69/70 Yield

Conditions & References

32 %, 10 %, 40 %

in diphenylether, heating to 155 deg C during 1 h Chandrasekharan, V.; Unnikrishnan, P.; Shah, G. D.; Bhattacharyya, S. C.; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 19; nb. 12; (1980); p. 1052 - 1055 View in Reaxys

O O HO

OH O

Rx-ID: 2163466 View in Reaxys 70/70 Yield

Conditions & References Time= 1h, T= 160 °C , pyrolysis; rate of decarboxylation, Product distribution Huneck, Siegfried; Schmidt, Juergen; Tabacchi, Raffaele; Zeitschrift fuer Naturforschung, B: Chemical Sciences; vol. 44; nb. 10; (1989); p. 1283 - 1289 View in Reaxys

26/26

2018-02-18 01:17:24