Piperazine → Piperidine

Participants

Reaction Steps

The secondary amine of a functionalized piperazine or piperidine can be alkylated with a haloacetonitrile under basic conditions to yield a cyanomethyl piperazine or piperidine analogue. In a typical procedure N-benzoyl piperazine was added to a solution of chloroacetonitrile and TEA in THF and stirred at r.t. for between 2 and 5 days. A resulting precipitate is removed by filtration, the filtrate is concentrated in vacuo, and the residue purified via chromatography to yield the cyanomethyl intermediate YCH2CN. The alkylation with haloacetonitrile can also be carried out with an alternate base, such as 4-methylmorpholine or diisopropylethyl amine.

Provenance & Evidence