4-fluoro-2-[(4-methoxyphenyl)methyl]phenol

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 23.66 g of 95% sodium hydride (0.94 mol) in 600 mL of dry toluene was added 100.0 g of 4-fluorophenol (0.89 mol) at 0° C. The mixture was stirred at 90° C. for 1 hour until gas evolution stopped. The mixture was cooled down to room temperature and a solution of 139.71 g of 3-methoxybenzyl chloride (0.89 mol) in 400 mL of dry toluene was added. After refluxing for 24 hours, the mixture was cooled to room temperature and quenched with 500 mL of water. The organic layer was separated, dried over MgSO4, and concentrated under high vacuum. The remaining starting materials were removed by distillation. The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane to yield 53.00 g (25.6%) of the product as a pink solid: 1H NMR (CDCl3) d 3.79 (s, 3H), 3.90 (s, 2H), 4.58 (s, 1H), 6.70-6.74 (m, 1H), 6.79-6.88 (m, 4H), 7.11-7.16 (m, 2H) The mixture was cooled down to room temperature After refluxing for 24 hours the mixture was cooled to room temperature quenched with 500 mL of water The organic layer was separated dried over MgSO4 concentrated under high vacuum The remaining starting materials were removed by distillation The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane

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

Procedure: To a solution of (2-benzyloxy-5-fluorophenyl)-(4-methoxyphenyl)-methanol (0.98 g, 2.90 mmol) in methanol (18.6 mL), a 20% palladium hydroxide catalyst (98 mg) was added and furthermore 2N—HCl (1 mL) was added thereto. The mixture was stirred under a hydrogen atmosphere for 15 hours, and then the catalyst was filtered off. The solvent was distilled under reduced pressure, and the obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:6)] to obtain the title compound (0.55 g, 82%). the catalyst was filtered off The solvent was distilled under reduced pressure the obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:6)]

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 23.66 g of 95% sodium hydride (0.94 mol) in 600 mL of dry toluene was added 100.0 g of 4-fluorophenol (0.89 mol) at 0° C. The mixture was stirred at 90° C. for 1 hour until gas evolution stopped. The mixture was cooled down to room temperature and a solution of 139.71 g of 3-methoxybenzyl chloride (0.89 mol) in 400 mL of dry toluene was added. After refluxing for 24 hours, the mixture was cooled to room temperature and quenched with 500 mL of water. The organic layer was separated, dried over MgSO4, and concentrated under high vacuum. The remaining starting materials were removed by distillation. The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane to yield 53.00 g (25.6%) of the product as a pink solid: 1H NMR (CDCl3) d 3.79 (s, 3H), 3.90 (s, 2H), 4.58 (s, 1H), 6.70-6.74 (m, 1H), 6.79-6.88 (m, 4H), 7.11-7.16 (m, 2H). The mixture was cooled down to room temperature After refluxing for 24 hours the mixture was cooled to room temperature quenched with 500 mL of water The organic layer was separated dried over MgSO4 concentrated under high vacuum The remaining starting materials were removed by distillation The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 23.66 g of 95% sodium hydride (0.94 mol) in 600 mL of dry toluene was added 100.0 g of 4-fluorophenol (0.89 mol) at 0° C. The mixture was stirred at 90° C. for 1 hour until gas evolution stopped. The mixture was cooled down to room temperature and a solution of 139.71 g of 3-methoxybenzyl chloride (0.89 mol) in 400 mL of dry toluene was added. After refluxing for 24 hours, the mixture was cooled to room temperature and quenched with 500 mL of water. The organic layer was separated, dried over MgSO4, and concentrated under high vacuum. The remaining starting materials were removed by distillation. The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane to yield 53.00 g (25.6%) of the product as a pink solid: 1H NMR (CDCl3) δ3.79 (s, 3H), 3.90 (s, 2H), 4.58 (s, 1H), 6.70-6.74 (m, 1H), 6.79-6.88 (m, 4H), 7.11-7.16 (m, 2H). The mixture was cooled down to room temperature After refluxing for 24 hours the mixture was cooled to room temperature quenched with 500 mL of water The organic layer was separated dried over MgSO4 concentrated under high vacuum The remaining starting materials were removed by distillation The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 23.66 g of 95% sodium hydride (0.94 mol) in 600 mL of dry toluene was added 100.0 g of 4-fluorophenol (0.89 mol) at 0° C. The mixture was stirred at 90° C. for 1 hour until gas evolution stopped. The mixture was cooled down to room temperature and a solution of 139.71 g of 3-methoxybenzyl chloride (0.89 mol) in 400 mL of dry toluene was added. After refluxing for 24 hours, the mixture was cooled to room temperature and quenched with 500 mL of water. The organic layer was separated, dried over MgSO4, and concentrated under high vacuum. The remaining starting materials were removed by distillation. The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane to yield 53.00 g (25.6%) of the product as a pink solid: 1H NMR (CDCl3) d 3.79 (s, 3H), 3.90 (s, 2H), 4.58 (s, 1H), 6.70-6.74 (m, 1H), 6.79-6.88 (m, 4H), 7.11-7.16 (m, 2H) The mixture was cooled down to room temperature After refluxing for 24 hours the mixture was cooled to room temperature quenched with 500 mL of water The organic layer was separated dried over MgSO4 concentrated under high vacuum The remaining starting materials were removed by distillation The crude dark red oil was filtered through a layer of 1 L of silica gel with neat hexane

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

Procedure: To a solution of (2-benzyloxy-5-fluorophenyl)-(4-methoxyphenyl)-methanol (0.98 g, 2.90 mmol) in methanol (18.6 mL), a 20% palladium hydroxide catalyst (98 mg) was added and furthermore 2N—HCl (1 mL) was added thereto. The mixture was stirred under a hydrogen atmosphere for 15 hours, and then the catalyst was filtered off. The solvent was distilled under reduced pressure, and the obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:6)] to obtain the title compound (0.55 g, 82%). the catalyst was filtered off The solvent was distilled under reduced pressure the obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:6)]