Water → 3-Bromo-5-[(1S)-2-tert-butoxy-1-methylethoxy]benzonitrile

Participants

Reaction Steps

To a stirred suspension of sodium bis(trimethylsilyl)amide (74.25 mmol; 14.33 g) in DMF (150 mL) at 23° C. was added (S)-tert-butoxy-2-propanol (74.25 mmoles, 9.82 g) over 15 minutes. A slight exotherm was observed (cold water cooling bath applied). A solution of 3-bromo-5-fluorobenzonitrile (49.50 mmol, 10.0 g) in DMF (40 mL) was added over 15 minutes with cold water bath still present. An exotherm (3° C.) was observed and the mixture turned from yellow to brown. DMF (10 mL) was added and the mixture stirred at ambient temperature for 1 hour. The reaction was quenched by addition of aqueous HCl (2M, 100 mL), maintaining temperature below 25° C. The mixture was diluted with water (200 mL) and extracted with 2:1 EtOAc/MTBE (3×200 mL). The organic layers were combined, washed with water (3×200 mL) and dried over MgSO4, and the solvent removed in vacuo affording the title compound as an orange oil (17.4 g). Further drying in vacuo at 23° C. gave the title product (15.5 g, ˜100%).

Provenance & Evidence