(4-methoxy-3-phenylmethoxyphenyl)methanol

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

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

Procedure: 121.1 mg (0.50 mmol) of 3-benzyloxy-4-methoxybenzaldehyde (7), 270 μL (15 mmol) of distilled water and stainless steel balls (50 pieces) were placed in the vessel of the planetary ball mill, which was then closed, and agitated by operating the planetary ball mill for 12 hours at 800 rpm (reversed every 30 minutes). After the lapse of 12 hours, 10 mL of ethyl acetate was added to the vessel of the ball mill to provide a solution containing the reaction mixture, which was then filtered with celite. The operation was repeated 5 times to provide a filtrate, which was then concentrated, thereby providing 74.0 mg (0.31 mmol) of 3-benzyloxy-4-methoxybenzyl alcohol (8) and 6.9 mg (0.05 mmol) of 3-hydroxy-4-methoxybenzyl alcohol (9). The yields were 61% and 9%, respectively. The reaction is expressed by the following scheme. 23.7 mg (0.10 mmol) of unreacted 3-benzyloxy-4-methoxybenzaldehyde (7) was recovered. was then closed for 12 hours to provide a solution containing the reaction mixture, which was then filtered with celite to provide a filtrate, which was then concentrated

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

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

Procedure: Thionyl chloride (64 ml) was added over 10 minutes to a stirred solution of the above alcohol in dichloromethane (500 ml). After 20 minutes the mixture was evaporated to dryness, in vacuo, toluene (2×75 ml) added, and evaporation in vacuo repeated to give crude 3-benzyloxy-4-methoxy-benzyl chloride (97.85 g, 105.5%). The chloride (353 mmole) was dissolved in acetone, (400 ml) treated with sodium thiocyanate, (57.22 g ,706 mmole) homogenized and heated under reflux for 1.5 hours. The solid was filtered off at room temperature and the solvent evaporated in vacuo. The residue was suspended in water (600 ml) to give a solution of pH 2, and neutralized with sodium bicarbonate solution. After crystallization the solid was collected, dried, dissolved in dichloromethane (300 ml) , dried (Na2SO4), treated with charcoal, filtered and evaporated to dryness. The residue was crystallized from petroleum ether (400 ml) to give 3-benzyloxy-4-methoxy-benzyl thiocyanate (95.65 g, 95.0%), mp 70-74° C. The thiocyanate (335 mmole) was heated under reflux in n-valeronitrile (280ml) for 2 hours and evaporated to dryness to give 98.4 g of crude product. This was dissolved in THF (200 ml) and treated with 32% aqueous ammonia solution (101 ml) at room temperature. After 3 hours the thiourea was collected at 10° C. and washed with diethyl ether to give 1-(3-benzyloxy-4-methoxy-benzyl)-2-thiourea (63.08 g, 62.2%), mp 179-181° C. The filtrate was evaporated to dryness and the residue crystallized from dichloromethane to give 11.51 g (11.3%) as a second crop. After 20 minutes the mixture was evaporated to dryness, in vacuo, toluene (2×75 ml) added evaporation in vacuo

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

Procedure: A solution of 3-hydroxy-4-methoxy-benzyl alcohol (61.67 g, 400 mmole) in 1-propanol (600 ml) was treated at 60° C. with 97% t-BuOK (55.52 g, 480 mmole), at 90° C. with benzyl chloride (66.57 ml, 560 mmole) and the resulting mixture heated under reflux for 2 hours. Then at 90° C. a second batch of t-BuOK (9.25 g, 80 mmole) was added. After a further hour at reflux a third batch of t-BuOK (9.25 g, 80 mmol) and a second batch of benzyl chloride (9.51 ml, 80 mmole) was added at 90° C. After a further 2.5 hours at reflux the mixture was cooled to room temperature and the solid filtered off. The solvents were removed in vacuo, the residue treated with water (300 ml) and one-third of the solvent removed in vacuo. Water (100 ml) was added to the residue, which was then distilled off in vacuo and the procedure repeated. The resulting suspension was filtered, the solid was collected, dried and triturated with petroleum ether (2×600 ml) to give 3-benzyloxy-4-methoxy-benzyl alcohol, (86.21 g, 88.2%) mp 62-65° C. the resulting mixture heated under reflux for 2 hours After a further 2.5 hours at reflux the mixture the solid filtered off The solvents were removed in vacuo the residue treated with water (300 ml) and one-third of the solvent removed in vacuo Water (100 ml) was added to the residue, which was then distilled off in vacuo The resulting suspension was filtered the solid was collected dried triturated with petroleum ether (2×600 ml)

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

Procedure: A solution of 0.35 mol of the compound obtained in Step 1 in 400 ml of methanol and 1.5 equivalents of sodium borohydride is stirred for 6 hours at ambient temperature and then 500 ml of acidified water are slowly added. The precipitate obtained is taken up in ether; the organic phase is subsequently extracted, dried, filtered and then evaporated off under reduced pressure, allowing the expected product to be isolated. The precipitate obtained the organic phase is subsequently extracted dried filtered evaporated off under reduced pressure to be isolated

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

Procedure: 121.1 mg (0.50 mmol) of 3-benzyloxy-4-methoxybenzaldehyde (7), 270 μL (15 mmol) of distilled water and stainless steel balls (50 pieces) were placed in the vessel of the planetary ball mill, which was then closed, and agitated by operating the planetary ball mill for 12 hours at 800 rpm (reversed every 30 minutes). After the lapse of 12 hours, 10 mL of ethyl acetate was added to the vessel of the ball mill to provide a solution containing the reaction mixture, which was then filtered with celite. The operation was repeated 5 times to provide a filtrate, which was then concentrated, thereby providing 74.0 mg (0.31 mmol) of 3-benzyloxy-4-methoxybenzyl alcohol (8) and 6.9 mg (0.05 mmol) of 3-hydroxy-4-methoxybenzyl alcohol (9). The yields were 61% and 9%, respectively. The reaction is expressed by the following scheme. 23.7 mg (0.10 mmol) of unreacted 3-benzyloxy-4-methoxybenzaldehyde (7) was recovered. was then closed for 12 hours to provide a solution containing the reaction mixture, which was then filtered with celite to provide a filtrate, which was then concentrated

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