4-methoxy-3-phenylmethoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound 3-hydroxy-4-methoxyphenyl 2-furoate was made as follows. An amount of 2.00 gms. of 3-benzyloxy-4-methoxyphenol, 1.00 gms. of triethylamine and 0.10 gms of 4-dimethylaminopyridine were dissolved in 100 ml. of methylene chloride at 0° C. and stirred. To the mixture was added 1.16 gms. of 2-furoyl chloride and the mixture was stirred overnight. The mixture was then washed wth equal volumes of 1 M hydrochloric acid, saturated sodium bicarbonate and water. The mixture was then dried over magnesium sulfate and the solvent evaporated to yield 3-benzyloxy-4-methoxyphenyl 2-furoate. To the mixture was added 1.16 gms The mixture was then washed wth equal volumes of 1 M hydrochloric acid, saturated sodium bicarbonate and water The mixture was then dried over magnesium sulfate the solvent evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound 3-hydroxy-4-methoxyphenyl 2-furoate was made as follows. An amount of 2.00 gms. of 3-benzyloxy-4-methoxyphenol, 1.00 gms. of triethylamine and 0.10 gms of 4-dimethylaminopyridine were dissolved in 100 ml. of methylene chloride at 0° C. and stirred. To the mixture was added 1.16 gms. of 2-furoyl chloride and the mixture was stirred overnight. The mixture was then washed wth equal volumes of 1 M hydrochloric acid, saturated sodium bicarbonate and water. The mixture was then dried over magnesium sulfate and the solvent evaporated to yield 3-benzyloxy-4-methoxyphenyl 2-furoate. To the mixture was added 1.16 gms The mixture was then washed wth equal volumes of 1 M hydrochloric acid, saturated sodium bicarbonate and water The mixture was then dried over magnesium sulfate the solvent evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound 3-hydroxy-4-methoxyphenyl benzoate was made as follows. An amount of 2.00 gms. of 3-benzyloxy-4-methoxyphenol, 1.00 gms. of triethylamine and 0.10 gms of 4-dimethylaminopyridine were dissolved in 100ml. of methylene chloride at 0° C. and stirred. To the mixture was added 1.22 gms. of benzoyl chloride and the mixture was stirred overnight. The mixture was then washed with equal volumes of 1M hydrochloric acid, saturated sodium bicarbonate and water. The mixture was then dried over magnesium sulfate and the solvent evaporated to yield 3-benzyloxy-4-methoxyphenyl benzoate. To the mixture was added 1.22 gms The mixture was then washed with equal volumes of 1M hydrochloric acid, saturated sodium bicarbonate and water The mixture was then dried over magnesium sulfate the solvent evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-benzyloxy-4-methoxyphenol (3 g) in DMSO (2 mL) was added potassium t-butoxide (1.6 g). After 30 min, 4-chloro-3,5-dimethyl-nitrobenzene (2 g) was added and the resulting solution was heated at 80° C. for 2 h. The reaction mixture was partitioned between ethyl acetate and 1 N aqueous NaOH, and the organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to afford 4-(3-benzyloxy-4-methoxyphenoxy)-3,5-dimethylnitrobenzene (1.9 g) as an orange solid. The reaction mixture was partitioned between ethyl acetate and 1 N aqueous NaOH the organic layer was washed with water, brine dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 3-benzyloxy-4-methoxybenzaldehyde (10 g) in MeOH (100 mL) was added hydrogen peroxide (5.5 mL of 30% aqueous) dropwise. After having been warmed to RT, concentrated sulfuric acid (1 mL) was added and the resulting solution was allowed to stir for 1.5 h. The reaction mixture was partitioned between ethyl ether/saturated aqueous sodium bicarbonate, another organic layer was dried over sodium sulfate and concentrated in vacuo to afford an oil. Flash chromatography (20% ethyl acetate/hexanes) afforded 3-benzyloxy-4-methoxyphenol (5.8 g). After having been warmed to RT The reaction mixture was partitioned between ethyl ether/saturated aqueous sodium bicarbonate another organic layer was dried over sodium sulfate concentrated in vacuo to afford an oil

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 3-benzyloxy-4-methoxybenzaldehyde (10 g) in MeOH (100 mL) was added hydrogen peroxide (5.5 mL of 30% aqueous) dropwise. After having been warmed to RT, concentrated sulfuric acid (1 mL) was added and the resulting solution was allowed to stir for 1.5 h. The reaction mixture was partitioned between ethyl ether/saturated aqueous sodium bicarbonate, another organic layer was dried over sodium sulfate and concentrated in vacuo to afford an oil. Flash chromatography (20% ethyl acetate/hexanes) afforded 3-benzyloxy-4-methoxyphenol (5.8 g). After having been warmed to RT The reaction mixture was partitioned between ethyl ether/saturated aqueous sodium bicarbonate another organic layer was dried over sodium sulfate concentrated in vacuo to afford an oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-chloroperoxybenzoic acid (9.9 g, 0.0343 mols), in small portions, is added to a stirred solution of 3-benzyloxy-4-methoxybenzaldehyde (201, prepared as described in Example 66) (7.57 g, 0.0313 mols) in dicloromethane (100 ml) over a thirty minute period With vigorous shirring. The reaction flask is fitted with a condensor and the contents is heated to reflux for six hours and monitored by TLC using 2:1 hexane-ethyl acetate as eluant. The reaction is filtered off the 3-chlorobenzoic acid (which precipitates out of solution) and the filtrate is washed with saturated sodium bicarbonate followed by water and dried in vacuo to an oil which eventually solidifies. The solid is subsequently dissolved in distilled methanol (80 ml) and heated to reflux under nitrogen. TLC using hexane-ethyl acetate as the eluant shows almost complete conversion after two hours and forty five minutes. The solvent is removed in vacuo no produce a dark oil which is redissolved in a small amount of ethyl acetate and purified by column chromatography on silica gel (2:1 hexane-ethyl acetate as eluant). The major fraction from the column is combined and concentrated in vacuo to a solid (4.68 g, 64.9%). The reaction flask is fitted with a condensor the contents is heated to reflux for six hours The reaction is filtered off the 3-chlorobenzoic acid (which precipitates out of solution) the filtrate is washed with saturated sodium bicarbonate dried in vacuo to an oil which The solid is subsequently dissolved in distilled methanol (80 ml) heated to reflux under nitrogen after two hours forty five minutes The solvent is removed in vacuo no produce a dark oil which purified by column chromatography on silica gel (2:1 hexane-ethyl acetate as eluant) concentrated in vacuo to a solid (4.68 g, 64.9%)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: FIGS. 17 and 18 disclose a procedure for synthesizing futoenone and futoenone derivative compounds. Benzyl bromide (BnBr) is used to protect isovanillin (201) by reaction using phase transfer conditions to yield 3-benzyloxy-4-methoxybenzaldehyde (202). Oxidation of 3-benzyloxy-4-methoxybenzaldehyde (202) with m-chloroperbenzoic acid followed by hydrolysis in refluxing methanol yields 3-benzyloxy-4-methoxyphenol (203). The phenol is placed in toluene and the suspension is treated with n-butyl-lithium to form a precipitate. 1,4-dibromobutene is then added to the reaction and the contents are heated to reflux overnight to form vinylbenzofuran (206). An ester (207) is formed using a Horner-Emmons modified Wittig reaction and is subsequently reduced to the allylic alcohol (208) using diisobutylaluminum hydride. The allylic alcohol can then be epoxidized in a Sharpless epoxidation to form 2-(2,3'-epoxybutanol)-7-benzyloxy-6-methoxydihydrobenzofuran (209).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound 3-hydroxy-4-methoxyphenyl benzoate was made as follows. An amount of 2.00 gms. of 3-benzyloxy-4-methoxyphenol, 1.00 gms. of triethylamine and 0.10 gms of 4-dimethylaminopyridine were dissolved in 100 ml. of methylene chloride at 0° C. and stirred. To the mixture was added 1.22 gms. of benzoyl chloride and the mixture was stirred overnight. The mixture was then washed with equal volumes of 1M hydrochloric acid, saturated sodium bicarbonate and water. The mixture was then dried over magnesium sulfate and the solvent evaporated to yield 3-benzyloxy-4-methoxyphenyl benzoate. To the mixture was added 1.22 gms The mixture was then washed with equal volumes of 1M hydrochloric acid, saturated sodium bicarbonate and water The mixture was then dried over magnesium sulfate the solvent evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 3-benzyloxy-4-methoxyphenol (3 g) in DMSO (2 mL) was added potassium t-butoxide (1.6 g). After 30 min, 4-chloro-3,5-dimethylnitrobenzene (2 g) was added and the resulting solution was heated at 80° C. for 2 h. The reaction mixture was partitioned between ethyl acetate and 1N aqueous NaOH, and the organic layer was washed with water, brine, dried over sodium sulfate and concentrated in vacuo to afford 4-(3-benzyloxy-4-methoxyphenoxy)-3,5-dimethylnitrobenzene (1.9 g) as an orange solid. The reaction mixture was partitioned between ethyl acetate and 1N aqueous NaOH the organic layer was washed with water, brine dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 3-benzyloxy-4-methoxybenzaldehyde (10 g) in MeOH (100 mL) was added hydrogen peroxide (5.5 mL of 30% aqueous) dropwise. After having been warmed to RT, concentrated sulfuric acid (1 mL) was added and the resulting solution was allowed to stir for 1.5 h. The reaction mixture was partitioned between ethyl ether/saturated aqueous sodium bicarbonate, another organic layer was dried over sodium sulfate and concentrated in vacuo to afford an oil. Flash chromatography (20% ethyl acetate/hexanes) afforded 3-benzyloxy-4-methoxyphenol (5.8 g). After having been warmed to RT The reaction mixture was partitioned between ethyl ether/saturated aqueous sodium bicarbonate another organic layer was dried over sodium sulfate concentrated in vacuo to afford an oil

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound 3-hydroxy-4-methoxyphenyl 2-furoate was made as follows. An amount of 2.00 gms. of 3-benzyloxy-4-methoxyphenol, 1.00 gms. of triethylamine and 0.10 gms of 4-dimethylaminopyridine were dissolved in 100 ml. of methylene chloride at 0° C. and stirred. To the mixture was added 1.16 gms. of 2-furoyl chloride and the mixture was stirred overnight. The mixture was then washed with equal volumes of 1M hydrochloric acid, saturated sodium bicarbonate and water. The mixture was then dried over magnesium sulfate and the solvent evaporated to yield 3-benzyloxy-4-methoxyphenyl 2-furoate. To the mixture was added 1.16 gms The mixture was then washed with equal volumes of 1M hydrochloric acid, saturated sodium bicarbonate and water The mixture was then dried over magnesium sulfate the solvent evaporated