Water → Methyl 2-(4-bromophenyl)acetate

Participants

Reaction Steps

To a suspension of 4-bromophenylacetic acid (2.15 g) and potassium carbonate (2.76 g) in N,N-dimethylformamide (15 mL) was added methyl iodide (0.94 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=10/1-5/1) to give methyl 4-bromophenylacetate (2.09 g). This material was dissolved in tetra hydrofuran (50 mL). To the solution was added methylmagnesium bromide (3.0 mol/L diethyl ether solution, 7.0 mL) under ice-cooling, and the mixture was stirred at the same temperature for 2 hours. To the reaction mixture was added 1 mol/L hydrochloric acid (30 mL), and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1-2/1) to give 1-bromo-4-[2-hydroxy-2-(methyl)propyl]benzene (1.58 g) This material was dissolved in N,N-dimethylformamide (20 mL) To the solution was added 55% sodium hydride (0.32 g) under ice-cooling, and the mixture was stirred at the same temperature for 10 minutes. To this mixture were added benzyl bromide (0.98 mL) and tetra(n-butyl)ammonium iodide (0.51 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=99/1-95/5) to give 4-[2-benzyloxy-2-(methyl)propyl]-1-bromobenzene (1.2 g). The title compound was prepared in a similar manner to that described in Step 2 of Reference Example 46 using this material instead of 1-bromo-2-fluoro-4-methoxy-benzene.

Provenance & Evidence