5-hydroxy-2-methoxybenzaldehyde

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:0.00; pressure:0.00; stir:

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

Procedure: To the Grignard reagent prepared from 4-bromoanisole (286 g) and magnesium turnings (38.5 g) in dry tetrahydrofuran (480 ml) was added, dropwise, with vigorous stirring, a solution of 5-hydroxy-2-methoxybenzaldehyde (100 g) in dry tetrahydrofuran (1 liter). The mixture was heated on a steam bath for 3 hours, cooled and decomposed with saturated ammonium chloride solution. The organic layer was removed and the aqueous extracted with ethyl acetate (twice). The combined organics were washed with water, dried with anhydrous magnesium sulphate and evaporated to dryness. The residue was stirred with water (4 liters), and the buff coloured solid collected and dried to give crude 1-(5-hydroxy-2-methoxyphenyl)-1-(4-methoxy- phenyl)-methanol (170 g, 99%), m.p. 62-68°. This carbinol (85 g) was dissolved in ethanol (700 ml) and 10% palladium on charcoal (10 g) added. The mixture was hydrogenated in a Parr apparatus at 45° until hydrogen uptake ceased. The mixture was filtered, the filtrate evaporated to dryness and the residue filtered through a column containing silica gel, eluting with dichloromethane, to give 2,4'-dimethoxy-5-hydroxydiphenylmethane (46 g, 58%), m.p. 56-58° (from petroleum spirit (60-80°)). was added The mixture was heated on a steam bath for 3 hours cooled The organic layer was removed the aqueous extracted with ethyl acetate (twice) The combined organics were washed with water dried with anhydrous magnesium sulphate evaporated to dryness collected dried

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

Procedure: To a stirred suspension of 5-hydroxy-2-methoxybenzaldehyde (306.6 g, prepared by the method of Ulrich et al, J. Org. Chem., 1974, 39, 2437), benzyl bromide (355.8 g) and Adogen 464 (48.5 g) in dichloromethane (600 ml) was added a solution of sodium hydroxide (123.5 g) in water (500 ml). The mixture became warm and the suspension dissolved; additional dichloromethane (300 ml) was added to prevent crystallisation of the benzylated product. After 2 hours, the organic layer was removed, washed twice with water, once with saturated sodium chloride solution, then dried with anhydrous magnesium sulphate The solution was concentrated, then treated with petroleum spirit to give 5-benzyloxy-2-methoxybenzaldehyde (445.7 g, 91%), m.p. 99-100°. prepared by the method of Ulrich et al, J The mixture became warm the suspension dissolved crystallisation of the benzylated product the organic layer was removed washed twice with water, once with saturated sodium chloride solution dried with anhydrous magnesium sulphate The solution was concentrated treated with petroleum spirit

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

Procedure: 6-(2-Bromo-5-hydroxyphenyl)hex-5-ene-2,4-dione (15 mg, 53 μmol) and boron trioxide (11 mg, 0.16 mmol) was placed in a 20 mL reaction vessel, and dissolved in 0.4 mL of ethyl acetate. To the stirring mixture at 80° C. was added a solution of 5-hydroxy-2-methoxybenzaldehyde (10 mg, 0.07 mmol) and tri-n-butyl borate (25 mL, 93 μmol), sequentially. After the reaction mixture was stirred for 2 h at the same temperature, n-butylamine (10 μL, 0.10 mmol) was added with additional stirring for 1 h. The reaction mixture was treated with a 1:1 solution (1 mL) of 1N HCl and brine at room temperature, and was stirred at 50° C. for 5 min to 1 h (if necessary, the reaction mixture was neutralized by saturated NaHCO3 aqueous solution). The organic layer was purified directly by silica gel column chromatography (eluting with hexane/ethyl acetate or chloroform/methanol) to obtain the title compound (2.2 mg, 10%) as a solid. was added was stirred at 50° C. for 5 min to 1 h (if necessary, the reaction mixture The organic layer was purified directly by silica gel column chromatography (eluting with hexane/ethyl acetate or chloroform/methanol)

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

Procedure: To the Grignard reagent prepared from 4-bromoanisole (286 g) and magnesium turnings (38.5 g) in dry tetrahydrofuran (480 ml) was added, dropwise, with vigorous stirring, a solution of 5-hydroxy-2-methoxybenzaldehyde (100 g) in dry tetrahydrofuran (1 liter). The mixture was heated on a steam bath for 3 hours, cooled and decomposed with saturated ammonium chloride solution. The organic layer was removed and the aqueous extracted with ethyl acetate (twice). The combined organics were washed with water, dried with anhydrous magnesium sulphate and evaporated to dryness. The residue was stirred with water (4 liters), and the buff coloured solid collected and dried to give crude 1-(5-hydroxy-2-methoxyphenyl)-1-(4-methoxy- phenyl)-methanol (170 g, 99%), m.p. 62-68°. This carbinol (85 g) was dissolved in ethanol (700 ml) and 10% palladium on charcoal (10 g) added. The mixture was hydrogenated in a Parr apparatus at 45° until hydrogen uptake ceased. The mixture was filtered, the filtrate evaporated to dryness and the residue filtered through a column containing silica gel, eluting with dichloromethane, to give 2,4'-dimethoxy-5-hydroxydiphenylmethane (46 g, 58%), m.p. 56-58° (from petroleum spirit (60-80°)). was added The mixture was heated on a steam bath for 3 hours cooled The organic layer was removed the aqueous extracted with ethyl acetate (twice) The combined organics were washed with water dried with anhydrous magnesium sulphate evaporated to dryness collected dried

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

Procedure: To a stirred suspension of 5-hydroxy-2-methoxybenzaldehyde (306.6 g, prepared by the method of Ulrich et al, J. Org. Chem., 1974, 39, 2437), benzyl bromide (355.8 g) and Adogen 464 (48.5 g) in dichloromethane (600 ml) was added a solution of sodium hydroxide (123.5 g) in water (500 ml). The mixture became warm and the suspension dissolved; additional dichloromethane (300 ml) was added to prevent crystallisation of the benzylated product. After 2 hours, the organic layer was removed, washed twice with water, once with saturated sodium chloride solution, then dried with anhydrous magnesium sulphate The solution was concentrated, then treated with petroleum spirit to give 5-benzyloxy-2-methoxybenzaldehyde (445.7 g, 91%), m.p. 99-100°. prepared by the method of Ulrich et al, J The mixture became warm the suspension dissolved crystallisation of the benzylated product the organic layer was removed washed twice with water, once with saturated sodium chloride solution dried with anhydrous magnesium sulphate The solution was concentrated treated with petroleum spirit

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

Procedure: To the Grignard reagent prepared from 4-bromoanisole (286 g) and magnesium turnings (38.5 g) in dry tetrahydrofuran (480 ml) was added, dropwise, with vigorous stirring, a solution of 5-hydroxy-2-methoxybenzaldehyde (100 g) in dry tetrahydrofuran (1 liter). The mixture was heated on a steam bath for 3 hours, cooled and decomposed with saturated ammonium chloride solution. The organic layer was removed and the aqueous extracted with ethyl acetate (twice). The combined organics were washed with water, dried with anhydrous magnesium sulphate and evaporated to dryness. The residue was stirred with water (4 liters), and the buff coloured solid collected and dried to give crude 1-(5-hydroxy-2-methoxyphenyl)-1-(4-methoxy- phenyl)-methanol (170 g, 99%), m.p. 62°-68°. This carbinol (85 g) was dissolved in ethanol (700 ml) and 10% palladium on charcoal (10 g) added. The mixture was hydrogenated in a Parr apparatus at 45° until hydrogen uptake ceased. The mixture was filtered, the filtrate evaporated to dryness and the residue filtered through a column containing silica gel, eluting with dichloromethane, to give 2,4'-dimethoxy-5-hydroxydiphenylmethane (46 g, 58%), m.p. 56°-58° (from petroleum spirit (60°-80°)). was added The mixture was heated on a steam bath for 3 hours cooled The organic layer was removed the aqueous extracted with ethyl acetate (twice) The combined organics were washed with water dried with anhydrous magnesium sulphate evaporated to dryness collected dried

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

Procedure: To a stirred suspension of 5-hydroxy-2-methoxybenzaldehyde (306.6 g, prepared by the method of Ulrich et al, J.Org.Chem., 1974, 39, 2437), benzyl bromide (355.8 g) and Adogen 464 (48.5 g) in dichloromethane (600 ml) was added a solution of sodium hydroxide (123.5 g) in water (500 ml). The mixture became warm and the suspension dissolved; additional dichloromethane (300 ml) was added to prevent crystallisation of the benzylated product. After 2 hours, the organic layer was removed, washed twice with water, once with saturated sodium chloride solution, then dried with anhydrous magnesium sulphate. The solution was concentrated, then treated with petroleum spirit to give 5-benzyloxy-2-methoxybenzaldehyde (445.7 g, 91%), m.p. 99°-100°. prepared by the method of Ulrich et al, J.Org.Chem The mixture became warm the suspension dissolved crystallisation of the benzylated product the organic layer was removed washed twice with water, once with saturated sodium chloride solution dried with anhydrous magnesium sulphate The solution was concentrated treated with petroleum spirit

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