1-Amino-2-propanol → 2-(4-chlorophenyl)-N-(2-hydroxypropyl)acetamide

Participants

Reaction Conditions

Reaction Steps

2-(4-Chlorophenyl)acetic acid (1.9 kg, 11.1 mol, 1.00 eq), toluene (1 L), phenylboronic acid (67 g, 549 mmo, 0.049 eq.), and boric acid (68 g, 1.10 mol. 0.099 eq) where charged to a 20 L jacketed reactor in the specified order. After the resulting mixture had been heated with stirring to 40° C., 1-amino-2-propanol (908 g, 12.09 mol, 1.085 eq) and toluene (1 L) were added. The reaction mixture was then heated to reflux while the water coproduct was removed in a Dean-Stark trap. Refluxing and water removal were continued until conversion of 2-(4-chlorophenyl)acetic acid exceeded 98%. Such conversion is usually achieved with 8-12 hours of refluxing. Water coproduct removed in the Dean-Stark trap totaled 265 mL (14.72 mol). After the reaction mixture had been cooled to 60-70° C., 5 wt % aqueous sodium bicarbonate (2 L) was added slowly while the reaction mixture was maintained at 60-70° C. Water (10 mL) was then added slowly while the stirred reaction mixture was maintained at ≧50° C. The diluted reaction mixture was cooled to 30° C. and stirred at that temperature for 30 minutes. The resulting solid precipitate was filtered and vacuum dried for 48 hours at 50° C. to provide 2-(4-chlorophenyl)-N-(2-hydroxypropyl)acetamide (2.356 kg, 92.9% yield not corrected for purity, 90.12% purity by HPLC peak area).

Provenance & Evidence