Hydrochloric Acid → methyl 2-(4-bromo-2-methylphenyl)acetate

Participants

Reaction Conditions

Reaction Steps

Potassium hydroxide (0.60 g, 11 mmol) was added to a solution of (4-bromo-2-methylphenyl)acetonitrile (1.0 g, 4.8 mmol) obtained in Example (17-1) in ethylene glycol (5 ml), and the mixture was stirred at 130° C. for 1.5 hours. After the reaction mixture was cooled to room temperature and concentrated hydrochloric acid was added to acidify the reaction mixture, the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. After the residue obtained by removing the solvent under reduced pressure was washed with water, it was dried under reduced pressure to give a solid. Potassium carbonate (0.97 g, 7.0 mmol) and methyl iodide (0.37 ml, 5.9 mmol) were added to a solution of the obtained solid in N,N-dimethylformamide (6 ml), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and the organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=99/1-10/1) to give crudely purified methyl (4-bromo-2-methylphenyl)acetate as an oil. According to a method similar to Example (8-1), from crude methyl (4-bromo-2-methylphenyl)acetate obtained in the above and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (814 mg, 3.7 mmol), methyl (4′-hydroxy-3-methyl-1,1′-biphenyl-4-yl)acetate was obtained as a colorless solid (0.70 g, three-step total yield: 56%).

Provenance & Evidence