1-bromo-4-(methoxymethyl)benzene

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: 4-Bromobenzyl alcohol (1.87 g) was added over 10 minutes to a stirred suspension of sodium hydride (0.24 g--used directly in the form of 0.48 g of a 50% dispersion in oil) in dry N,N-dimethylformamide (10 cm3) under an atmosphere of nitrogen. Afer evolution of hydrogen had ceased (20 minutes), methyl iodide (1.42 g) was added and the reaction mixture was stirred for a further 10 minutes. The mixture was poured into water and the organic layer separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were dried over anhydrous sodium sulphate, and concentrated by evaporation under reduced pressure. The residual, crude product was purified by column chromatography on a silica gel support, eluting with n-hexane containing 12.5% by volume ethyl acetate, to give 4-bromobenzyl methyl ether (1.6 g). was added the organic layer separated The aqueous layer was extracted with diethyl ether The combined organic layers were dried over anhydrous sodium sulphate concentrated by evaporation under reduced pressure The residual, crude product was purified by column chromatography on a silica gel support eluting with n-hexane containing 12.5% by volume ethyl acetate

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

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

Procedure: To a suspension of 60% sodium hydride (1.6 g) in dimethylformamide (50 ml) was added 4-bromobenzyl alcohol (5.00 g) under ice-water cooling and the mixture was stirred at 0° C. for 0.5 hour. To the mixture was added methyl iodide (2 ml) under ice-water cooling and the mixture was stirred at 0° C. for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with hexane to give 4-(methoxymethyl)bromobenzene as colorless oil (3.63 g). the mixture was stirred at 0° C. for 1 hour The mixture was partitioned between ethyl acetate and water The organic layer was separated washed with water and brine dried over magnesium sulfate evaporated in vacuo The residue was purified by silica gel column chromatography eluting with hexane

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

Procedure: To a suspension of 60% sodium hydride (1.6 g) in dimethylformamide (50 ml) was added 4-bromobenzyl alcohol (5.00 g) under ice-water cooling and the mixture was stirred at 0° C. for 0.5 hour. To the mixture was added methyl iodide (2 ml) under ice-water cooling and the mixture was stirred at 0° C. for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with hexane to give 4-(methoxymethyl)bromobenzene as colorless oil (3.63 g). the mixture was stirred at 0° C. for 1 hour The mixture was partitioned between ethyl acetate and water The organic layer was separated washed with water and brine dried over magnesium sulfate evaporated in vacuo The residue was purified by silica gel column chromatography eluting with hexane

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

Procedure: 4-Bromobenzyl alcohol (1.87 g) was added over 10 minutes to a stirred suspension of sodium hydride (0.24 g--used directly in the form of 0.48 g of a 50% dispersion in oil) in dry N,N-dimethylformamide (10 cm3) under an atmosphere of nitrogen. Afer evolution of hydrogen had ceased (20 minutes), methyl iodide (1.42 g) was added and the reaction mixture was stirred for a further 10 minutes. The mixture was poured into water and the organic layer separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were dried over anhydrous sodium sulphate, and concentrated by evaporation under reduced pressure. The residual, crude product was purified by column chromatography on a silica gel support, eluting with n-hexane containing 12.5% by volume ethyl acetate, to give 4-bromobenzyl methyl ether (1.6 g). was added the organic layer separated The aqueous layer was extracted with diethyl ether The combined organic layers were dried over anhydrous sodium sulphate concentrated by evaporation under reduced pressure The residual, crude product was purified by column chromatography on a silica gel support eluting with n-hexane containing 12.5% by volume ethyl acetate

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

Procedure: 4-Bromobenzyl alcohol (1.87 g) was added over 10 minutes to a stirred suspension of sodium hydride (0.24 g--used directly in the form of 0.48 g of a 50% dispersion in oil) in dry N,N-dimethylformamide (10 cm3) under an atmosphere of nitrogen. Afer evolution of hydrogen had ceased (20 minutes), methyl iodide (1.42 g) was added and the reaction mixture was stirred for a further 10 minutes. The mixture was poured into water and the organic layer separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were dried over anhydrous sodium sulphate, and concentrated by evaporation under reduced pressure. The residual, crude product was purified by column chromatography on a silica gel support, eluting with n-hexane containing 12.5% by volume ethyl acetate, to give 4-bromobenzyl methyl ether (1.6 g). was added the organic layer separated The aqueous layer was extracted with diethyl ether The combined organic layers were dried over anhydrous sodium sulphate concentrated by evaporation under reduced pressure The residual, crude product was purified by column chromatography on a silica gel support eluting with n-hexane containing 12.5% by volume ethyl acetate

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: In THF (200 ml) was dissolved 4-bromobenzyl alcohol (19.8 g), and to the solution was added under ice-cooling 65% sodium hydride (3.6 g). The mixture was stirred at room temperature for 30 minutes, and to the mixture was added dropwise under ice-cooling iodomethane (8.0 ml). The mixture was stirred at room temperature for 2 hours. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column chromatography (hexane/ethyl acetate=12/1) to give 1-bromo-4-(methoxymethyl)benzene (14.8 g). In THF (10 ml) was dissolved 1-bromo-4-(methoxymethyl)benzene (12.8 g), and to the mixture was added dropwise at−78° C. 1.6M n-butyllithium/hexane (42.4 ml). The mixture was stirred for 1 hour, and to the mixture was added dropwise a solution of trimethyl borate (19.2 g) in THF (38.4 ml). The mixture was stirred for30 minutes and warmed to room temperature. To the mixture was added 5% sulfuric acid (124 ml), and the mixture was stirred for 15 minutes. The reaction mixture was extracted with ethyl acetate, washed with saturated brine and dried with magnesium sulfate. Under reduced pressure, the solvent was evaporated, and the residue was washed with hexane/isopropylether to give 4-(methoxymethyl)phenyl borate (6.3 g). to the solution was added under ice- to the mixture was added dropwise under ice- The mixture was stirred at room temperature for 2 hours the mixture was extracted with ethyl acetate washed with saturated brine dried with magnesium sulfate Under reduced pressure, the solvent was evaporated the residue was purified with silica gel column chromatography (hexane/ethyl acetate=12/1)