N-Benzylnormechlorethamine → 2,2'-((Phenylmethyl)imino)bisethanol

Participants

Reaction Steps

In one of its aspects, the invention resides in an improved process for preparing N,N-bis(2-chloroethyl)benzylamine by first reacting benzyl chloride with bis(2-hydroxyethyl)amine to produce N,N-bis(2-hydroxyethyl)benzylamine and then reacting N,N-bis(2-hydroxyethyl)benzylamine with thionyl chloride to produce N,N-bis(2-chloroethyl)benzylamine, wherein the improvements comprise adding about one molar equivalent of benzyl chloride to a warmed mixture containing about one molar equivalent of N,N-bis(2-hydroxyethyl)amine and about one molar equivalent of sodium carbonate, the addition rate of benzyl chloride being so as to maintain the exothermic reaction temperature at about 70°-100° C.; maintaining the reaction temperature at about 70° to 100° C. for a short period; adding toluene to the reaction mixture; separating and drying the toluene solution containing N,N-bis(2-hydroxyethyl)benzylamine; adding said dry toluene solution to more than two molar equivalents of thionyl chloride heated to about 65° to 75° C., the rate of addition being so as to maintain the reaction temperature at about 65°-75° C.; treating the reaction mixture with aqueous alkali; and, separating the toluene solution containing a substantially quantitative yield of N,N-bis(2-chloroethyl)benzylamine, which can be used directly in the next step of the synthesis of 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride.

Provenance & Evidence