CA2393559C — Methods for the syntheses of alfentanil, sufentanil and remifentanil

USPTO Abstract

Synthetic pathways are disclosed for synthesizing derivatives or analogs of fentanyl. Specifically set out are pathways for synthesizing alfentanil, sufentanil and remifentanil. The disclosed methods require fewer steps and produce a greater yield of product than methods reported in the prior art. The pathways to all these compounds begin with a common pathway of condensing a piperidone with a primary amine so as to form a 4-amino-4-carboxyamino- piperidine, wherein N of said piperidone is a-N-COO- (CH2)n CH3, alkylating an N of said primary amine which was condensed with said piperidone thereby producing an N-alkyl-anilide, and hydrolyzing said -COO-(CH2)n CH3 group of said 4-amino-4-carboxyamino- piperidine following the condensation reaction so as to form a piperidine hydrolysis product. This product can then be converted to remifentanil in a 4 step reaction. Also, this hydrolysis product can be treated with a hydride to yield a 4-hydroxymethyl-piperidine which can be converted to alfentanil in 3 further steps, to sufentanil in 3 more steps, or to a variety of remifentanil analogs in tw o steps.