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)nCH3, alkylating an N of said primary amine which was condensed with said piperidone thereby producing an N-alkyl-anilide, and hydrolyzing said -COO-(CH2)nCH3 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 two steps.
Patent WO0140184
See also: Post 379262
(pHarmacist: "Preparation of piperidine derivatives, sufentanil", Methods Discourse)
