Sodium hydride → (R)-tert-Butoxycarbonylamino-[4-(2-methoxy-ethoxy)-phenyl]-acetic acid

Participants

Reaction Steps

To a mechanically stirring solution of (R)-tert-butoxycarbonylamino-(4-hydoxy-phenyl)-acetic acid (37.41 g, 140 mmol) (pepared according to the procedure of Salituro, G. M.; Townsend, C. A. J. Am. Chem. Soc. 1990, 112, 760) in N,N-dimethylformamide (750 mL) cooled in a dry ice/acetone bath was added sodium hydride (60% suspension in mineral oil) (12.32 g, 308 mmol) in small portions. The mixture was stirred while cooling in a dry ice/acetone bath for 30 minutes, then a solution of bromoethyl methyl ether (19.73 mL, 210 mmol) in N,N-dimethylformamide (200 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 24 hours. The reaction mixture was diluted with ice-water and extracted with ethyl acetate. The aqueous layer was cooled in an ice bath and acidified using concentrated aqueous hydrochloric acid to pH=1. The resulting mixture was extracted with ethyl acetate (3×), the organic extracts were combined, washed with water, brine and dried over sodium sulfate. Evaporation of the solvents gave (R)-tert-butoxycarbonylamino-{4-[2-(methoxy)-ethoxy]-phenyl}-acetic acid as a white solid (35.7 g, 78%).

Provenance & Evidence