Sodium Cyanide → Ethyl 4-cyano-4-(4-fluoroanilino)piperidine-1-carboxylate

Participants

Reaction Steps

75 Parts of ethyl 4-oxo-1-piperidinecarboxylate and 50 parts of 4-fluorobenzeneamine are added dropwise to 220 parts of acetic acid. The whole is stirred for 30 minutes. Then there is added dropwise a solution of 23 parts of sodium cyanide in 65 parts of water at room temperature (exothermic reaction). Upon completion, a second portion of 2 parts of sodium cyanide is added and the whole is stirred overnight. The reaction mixture is poured onto a mixture of 440 parts of water, 440 parts of ammonium hydroxide solution and 525 parts of trichloromethane. The trichloromethane-phase is separated and the aqueous layer is extracted with trichloromethane. The combined organic layers are washed with water, dried and evaporated, yielding 127.5 parts of ethyl 4-cyano-4-(4-fluorophenylamino)-1-piperidinecarboxylate as a residue.

Provenance & Evidence