Hydrochloric Acid → Florfenicol amine

Participants

Reaction Steps

(4S,5R)-3-acetyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound IX: R1 is methylsulfonyl; R2, R3 and R4 are methyl) (50.0 g, 0.1518 moles) hydrolyses in water (300 mL) containing 20% hydrochloric acid at 90 to 100° C. over about 1 hour. Washing with methylene chloride (200 mL), adjusting the pH to greater than 12 by addition of sodium hydroxide and extraction with methylene chloride (300 mL) yields (1R,2S)-1-[4-(methylsulfonyl)phenyl]-2-amino-3-fluoro-1-propanol (Compound Xa) in solution. Methanol (100 mL) replaces methylene chloride which distills off. Addition of methyl dichloroacetate (65.1 g, 0.4554 moles) and triethylamine (16.1 g, 0.1594 moles) with agitation for 12-16 hours at 20-25° C. then addition of water (175 mL) and toluene (100 mL) precipitates the crude product. Filtration, washing with water (100 mL) and toluene (174 mL) then dissolution in water (115 mL) and isopropanol (115 mL) at reflux, cooling to 20-25° C., filtration of the solids, washing with 1 to 1 water/isopropanol (50 mL) then drying gives pure (1R,2S)-2-dichloroacetamido-3-fluoro-1-[4-(methylsulfonyl)phenyl]-1-propanol (Florfenicol).

Provenance & Evidence