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. Adjusting the pH to greater than 12 by addition of sodium hydroxide and extraction with methylene chloride (500 mL) yields (1R,2S)-1-[4-(methylsulfonyl)phenyl]-2-amino-3-fluoro-1-propanol (Compound Xa) in solution. Addition of triethylamine (16.9 g, 0.1670 moles) and dichloroacetyl chloride (24.6 g, 0.1670 moles) at 20-30° C. for 4-6 hours then removal of methylene chloride by distillation and replacement by toluene (350 mL) and water (100 mL) precipitates the product. Filtration, washing with water (150 mL) and toluene (150 mL) then drying yields (1R,2S)-2-dichloroacetamido-3-fluoro-1-[4-(methylsulfonyl)phenyl]-1-propanol (Florfenicol).

Provenance & Evidence