(3-bromo-4-methoxyphenyl)methanol

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: 3-Bromo-4-hydroxybenzyl alcohol (1.22 g, 6.0 mmol) prepared from i) and sodium methoxide (0.36 g, 6.6 mmol) as base were added to N,N-dimethylformamide (100 ml), and the mixture was stirred for 30 min at room temperature. Chloromethyl resin (Merrifield resin, 1 mmol of chloromethyl site, formula 4; 1.22 g, 2.0 mmol) was added to the reaction solution and stirred for 24 hr at 50° C. The same was filtrated and washed repeatedly with water, methanol and dichloromethane. IR and XPS analyses were performed. stirred for 24 hr at 50° C The same was filtrated washed repeatedly with water, methanol and dichloromethane

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9.8 g (42 mmol) of 3-bromo-4-methoxybenzoic acid in THF (100 mL) was added 1M solution of borane in THF (130 mL) at r.t. under nitrogen. The resulting solution was then heated at 75° C. for 30 min. The reaction mixture was then cooled to r.t. and MeOH (0.5 mL) was slowly added. The mixture was concentrated and successively treated with MeOH (0.5 mL), evaporated (2×) and finally triturated with Et2O and filtered to yield the title product as a solid, m.p.: 49°-54° C. The reaction mixture was then cooled to r.t. The mixture was concentrated successively treated with MeOH (0.5 mL) evaporated (2×) finally triturated with Et2O filtered

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9.8 g (42 mmol) of 3-bromo-4-methoxybenzoic acid in THF (100 mL) was added 1M solution of borane in THF (130 mL) at r.t. under nitrogen. The resulting solution was then heated at 75° C. for 30 min. The reaction mixture was then cooled to r.t. and MeOH (0.5 mL) was slowly added. The mixture was concentrated and successively treated with MeOH (0.5 mL), evaporated (2×) and finally triturated with Et2O and filtered to yield the title product as a solid, m.p.: 49°-54° C. The reaction mixture was then cooled to r.t. The mixture was concentrated successively treated with MeOH (0.5 mL) evaporated (2×) finally triturated with Et2O filtered

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 a solution of 98.8 g of the compound obtained in Step 204-1 in DMF (455 ml) was added 72.0 g of TBSCl and 62.0 g of imidazole under ice cooling, and the reaction mixture was stirred for 10 minutes. The solution was warmed to room temperature then stirred for two hours, water and Et2O were added and liquid separation was performed. The organic layer was washed with saturated brine and dried over MgSO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. n-hexane was used on the obtained solid residue for a recovery by filtration to obtain 152 g of the title compound. then stirred for two hours liquid separation The organic layer was washed with saturated brine dried over MgSO4 the drying agent was separated by filtration the solvent was evaporated under reduced pressure n-hexane was used on the obtained solid residue for a recovery by filtration

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

Procedure: To a mixed solution of 100 g of 3-bromo-para-anisaldehyde in MeOH (700 ml) and THF (100 ml), on ice, was added 7.50 g of NaBH4. After the solution was warmed to room temperature and stirred for two hours, acetone was added. The reaction solution was concentrated under reduced pressure, water and EtOAc were added to the residue, and liquid separation was performed. The organic layer was washed with saturated brine and dried over MgSO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60; mobile phase: EtOAc/n-hexane=1/1; v/v) to obtain 99.8 g of the title compound (colorless solid). The reaction solution was concentrated under reduced pressure, water and EtOAc were added to the residue, and liquid separation The organic layer was washed with saturated brine dried over MgSO4 the drying agent was separated by filtration the solvent was evaporated under reduced pressure The obtained residue was purified by column chromatography (silicagel 60; mobile phase: EtOAc/n-hexane=1/1; v/v)

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

Procedure: To a solution of 3-bromo-4-methoxybenzaldehyde (4.98 g) in ethanol (50 mL) and tetrahydrofuran (10 mL) was added sodium borohydride (1.31 g) under ice-water cooling. The mixture was stirred at 0° C. for 2 hours. After evaporation of the solvent, the residue was partitioned between ethyl acetate and water. The separated organic layer was washed successively with water and brine, and dried over magnesium sulfate. The organic layer was evaporated in vacuo to give 3-bromo-4-methoxybenzyl alcohol as a colorless oil (4.98 g). After evaporation of the solvent the residue was partitioned between ethyl acetate and water The separated organic layer was washed successively with water and brine dried over magnesium sulfate The organic layer was evaporated in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 9.8 g (42 mmol) of 3-bromo-4-methoxybenzoic acid in THF (100 mL) was added 1M solution of borane in THF (130 mL) at r.t. under nitrogen. The resulting solution was then heated at 75° C. for 30 min. The reaction mixture was then cooled to r.t. and MEOH (0.5 mL) was slowly added. The mixture was concentrated and successively treated with MEOH (0.5 mL), evaporated (2×) and finally triturated with Et2O and filtered to yield the title product as a solid, m.p.: 49°-54° C. The reaction mixture was then cooled to r.t. MEOH (0.5 mL) was slowly added The mixture was concentrated successively treated with MEOH (0.5 mL) evaporated (2×) finally triturated with Et2O filtered

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

Procedure: To a solution of (3-bromo-4-methoxy-phenyl)-methanol (500 mg, 2.304 mmol, example 28) in tetrahydrofuran (5 mL) cooled to 0° C. was added sodium hydride (70 mg, 2.765 mmol). After 5 min, methyl iodide (287 μL, 4.608 mmol) was added. The reaction was then stirred at room temperature for 30 min. Thin layer chromatography (KP-Sil™ 32-63 μm, 60 Å silica gel, 40% ethyl acetate in hexanes) showed a mixture of starting material and product (higher Rf spot). Additional sodium hydride (58 mg) and methyl iodide (0.287 μL) were added and the reaction mixture was stirred at room temperature for 12 h. Water (5 mL) was added to quench the excess sodium hydride and the product was extracted with diethyl ether (2×50 mL). The organic layers were washed with brine (1×5 mL) and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 20% ethyl acetate in hexanes yielded 2-bromo-1-methoxy-4-methoxymethyl-benzene (467 mg, 88%). a mixture of starting material and product (higher Rf spot) the reaction mixture was stirred at room temperature for 12 h to quench the excess sodium hydride the product was extracted with diethyl ether (2×50 mL) The organic layers were washed with brine (1×5 mL) dried over anhydrous sodium sulfate The solid was then filtered off the filtrate was concentrated in vacuo Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 20% ethyl acetate in hexanes