321430-28-8

Questions And Answer

• Synthesis

  To a solution of 3-flfluoroaniline (50.0 g, 450 mmol) in CH2Cl2 (200 mL) was added a solution of potassium carbonate (46.9 g, 339 mmol) in water (200 mL) at  room temperature. The mixture was warmed to 32 ºC, and isobutyl chloroformate (66.2 g, 485 mmol) was added over 13 min while maintaining the temperature at  30−35 ºC. The mixture was stirred at 30−35 ºC for 2.5 h until complete by GC  analysis. Aqueous ammonia (29.3 wt%, 7.2 mL, 111 mmol) was added and the mixture stirred at 30−35 ºC for 15 min. The mixture was cooled to 25 ºC and the  pH adjusted from 8.7 to 1.9 with concentrated hydrochloric acid. The phases were separated, and the aqueous layer was washed with CH2Cl2 (100 mL). The combined organics were washed with water (200 mL), and the water was back-extracted with CH2Cl2 (100 mL). Typically, the crude product was carried into the next step but, if desired, crystallization at this point from heptane at −30 ºC afforded the amide (93.1 g, 98.1%).
  
  Reference: Herrinton, P. M.; Owen, C. E.; Gage, J. R. Org. Process Res. Dev. 2001, 5, 80–83.;