2-(4-methoxyphenyl)ethanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 100 g (0.60 mol) of p-methoxyphenylacetic acid in ether is introduced into a 4 l reactor, under nitrogen, which contains 28 g (0.74 mol) of lithium aluminum hydride and 600 ml of anhydrous ether. The mixture is heated under reflux for 3 hours and then cooled in a bath of ice and salt and the excess hydride is removed by cautiously adding 25 ml of water, followed by 25 ml of 15% strength NaOH and, finally, 20 ml of water. The white precipitate is removed by filtration, and after evaporation of the ether, 80 g of an oil are obtained. This oil, when distilled under 0.07 mm Hg at a temperature of 115° C., gives 77 g of 2-(p-methoxyphenyl)-ethan-1-ol. Yield: 85%. The mixture is heated under reflux for 3 hours cooled in a bath of ice and salt the excess hydride is removed by cautiously adding 25 ml of water The white precipitate is removed by filtration after evaporation of the ether, 80 g of an oil are obtained This oil, when distilled under 0.07 mm Hg at a temperature of 115° C.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Tributyl phosphoranylidene)acetonitrile (428 μL, 1.50 mmol) was added to a solution of toluene (7 mL) containing N-(4-hydroxybenzoyl)glycine tert-butyl ester (264 mg, 1.05 mmol) prepared in Example 1 (1a) and 2-(4-methoxyphenyl)ethanol (176 mg, 1.16 mmol). The mixture was stirred at 100° C. for 3.5 hours, and then water was added thereto. The mixture was extracted with ethyl acetate. The organic layers were combined, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was purified by silica gel column chromatography (hexane to hexane:ethyl acetate, 6:1, 4:1, and 3:1, v/v) to give an oily substance (358 mg). To a solution of dichloromethane (1 mL) containing this oily substance (358 mg, 0.929 mmol), trifluoroacetic acid (0.5 mL) was added. The mixture was stirred at room temperature for 1 hour, and then the solvent was evaporated. Diisopropyl ether was added to the resulting residue to suspend it. The produced precipitate was collected by filtration and was washed with diisopropyl ether to give 248 mg of the title compound (colorless crystalline solid, yield: 72%). The mixture was extracted with ethyl acetate washed with water and saturated brine dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was purified by silica gel column chromatography (hexane to hexane ethyl acetate, 6:1, 4:1, and 3:1, v/v) to give an oily substance (358 mg) was added The mixture was stirred at room temperature for 1 hour the solvent was evaporated Diisopropyl ether was added to the resulting residue The produced precipitate was collected by filtration was washed with diisopropyl ether

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

Procedure: A mixture of 4-methoxybenzeneethanol (7.0 g), 1,5-dibromopentane (20 ml), 50% aqueous sodium hydroxide (30 ml) and tetrabutylammonium bisulphate (1 g) was stirred at room temperature overnight, water (100 ml) wa added and the mixture was extracted with ER (2×100 ml). The organic extracts were washed with water and brine, dried and concentrated in vacuo to give an oil which was purified by FCC eluting with hexane→hexane-ER (9:1) to give the title compound as a colourless liquid (10.5 g). T.l.c. hexane-ER (9:1) Rf 0.28. the mixture was extracted with ER (2×100 ml) The organic extracts were washed with water and brine dried concentrated in vacuo to give an oil which was purified by FCC eluting with hexane→hexane-ER (9:1)

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

Procedure: 4-Methoxyphenethyl alcohol (50 g) and triphenylphosphine (103 g) were dissolved in methylene chloride (600 ml), followed by the addition of N-bromosuccinimide (70 g) in small portions under ice-cooling, and the resulting mixture was stirred at room temperature for 30 min. The reaction mixture was evaporated, and to the resulting residue was added hexane. The insoluble matters were filtered off, while the resulting filtrate was evaporated, to give the title compound as a colorless oil (50.32 g, yield; 71%). cooling The reaction mixture was evaporated to the resulting residue was added hexane The insoluble matters were filtered off, while the resulting filtrate was evaporated

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

Procedure: 4-Methoxyphenethyl alcohol (50 g) and triphenylphosphine (103 g) were dissolved in methylene chloride (600 ml), followed by the addition of N-bromosuccinimide (70 g) in small portions under ice-cooling, and the resulting mixture was stirred at room temperature for 30 min. The reaction mixture was evaporated, and to the resulting residue was added hexane. The insoluble matters were filtered off, while the resulting filtrate was evaporated, to give the title compound as a colorless oil (50.32 g, yield; 71%). cooling The reaction mixture was evaporated to the resulting residue was added hexane The insoluble matters were filtered off, while the resulting filtrate was evaporated

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

Procedure: 4-Methoxybenzeneethanol (5.0 g) and 1,6-dibromohexane (23.7 g) were stirred rapidly at RT with tetra-n-butyl ammonium bisulphate (0.94 g) and 12.5M aqueous NaOH (30 ml) for 16 h. The mixture was diluted with H2O (125 ml), extracted with ER (3×150 ml) and the combined organic extracts were washed consecutively with H2O (125 ml), BR (125 ml), dried and evaporated to give an oil (24.6 g). The oil was purified by [FCS] eluting with ER-CX (0:100→4:96) to give the title compound as a colourless oil (8.30 g). T.l.c. (CX-ER (40:1)) Rf 0.33. extracted with ER (3×150 ml) the combined organic extracts were washed consecutively with H2O (125 ml), BR (125 ml) dried evaporated