Pyridine → (2S)-1-Acetamido-3-chloropropan-2-yl acetate

Participants

Reaction Conditions

Reaction Steps

To a slurry of (S)-1-amino-3-chloro-2-propanol hydrochloride (500 g, 3.43 mol) in methylene chloride (1.54 kg) and acetic anhydride (803 g, 7.87 mol) is added pyridine (340 g, 4.3 mol) over 1 h while maintaining 38 to 46° C. The mixture is then stirred at 21 to 46° C. for 22 h. Water (600 ml) is added at 22 to 24° C. then aqueous potassium carbonate (47 wt %, 2.0 kg, 6.80 mol) while maintaining 6 to 11° C. Water (600 ml) and methylene chloride (600 ml) are added and the phases separated at 24° C. The aqueous is washed with methylene chloride (600 ml) and the combined organics concentrated under reduced pressure to 1.3 liter total volume. Toluene (2×1.0 liter) was added and the mixture concentrated to 1.4 liter after each addition. The mixture is cooled to 24° C. and isooctanes (2.3 liter) added. The resultant slurry is cooled to 0° C. and the precipitate collected by vacuum filtration, washed with isooctanes (700 ml) and dried in a nitrogen stream to give the title compound. This compound can also be prepared according to the procedures disclosed in WO 9924393 or Tetrahedron Letters, Vol. 37, No. 44, pp. 7937-7940.

Provenance & Evidence