Hydrochloric Acid → 5,5-Difluoro-4-[[(phenylmethoxy)carbonyl]amino]pentanoic acid

Participants

Reaction Steps

To a solution of 2 mmole of 4-amino-4-difluoromethylbutyric acid in 5 ml of 1 N sodium hydroxide at 0° C. are added simultaneously from two syringes 2 mmole of benzyl chloroformate in 1 ml of dioxane and 2 ml of 1 N sodium hydroxide. After 30 minutes at 0° C. the solution is acidified by the addition of 6 N hydrochloric acid, then extracted well with dichloromethane. The organic phase is dried and concentrated to afford 4-benzyloxycarbonylamino-4-difluoromethylbutyric acid which is dissolved in 15 ml of dichloromethane and treated with 2 mmole of thionyl chloride at 25° C. for 1 hour after which 4 mmole of propyl amine is added. The solution is stirred at 25° C. for one hour, then washed with water, dried and concentrated. The residue is treated with 6 ml of a solution of dioxane containing 40% w/w hydrogen bromide and allowed to stand for 30 minutes at 25° C. after which 50 ml of ether is added. The resulting precipitate is collected to afford N-propyl 4-amino-4-difluoromethylbutyramide hydrobromide.

Provenance & Evidence