Mallinckrodt, Inc.

Douglas C Miller

Esa T Jarvi

Peter Xianqi Wang

Frank William Moser

David W Berberich

Subo Liao

Robert E Halvachs

The present invention provides processes for the preparation of N-alkyl morphinans without the isolation of nor-morphinan intermediates. In particular, the invention provides tandem hydrolysis/alkylation reactions for the synthesis of N-alkyl morphinans.

Tandem process for preparing N-alkyl morphinans

An improved process for the preparation of a heteroaryl acetamide from a heteroaryl &#x3b1;-hydroxyacetamide is provided. The process comprises directly hydrogenating the heteroaryl &#x3b1;-hydroxyacetamide in the presence of a strong acid, a halide and a catalyst wherein the molar ratio of the starting heteroaryl &#x3b1;-hydroxyacetamide to water at the initiation of hydrogenolysis is at least about 2:1. In one embodiment, the heteroaryl acetamide is zolpidem and the heteroaryl &#x3b1;-hydroxyacetamide is &#x3b1;-hydroxyzolpidem.

Synthesis of heteroaryl acetamides from reaction mixtures having reduced water content

An improved process for the preparation of a heteroaryl acetamide from a heteroaryl &#x3b1;-hydroxyacetamide is provied. The process comprises directly hydrogenating the heteroaryl &#x3b1;-hydroxyacetamide in the presence of a strong acid, a halide and a catalyst. In one embodiment, the heteroaryl acetamide is zolpidem and the heteroaryl &#x3b1;-hydroxyacetamide is &#x3b1;-hydroxyzolpidem.

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University City, MO, United States of America

Douglas C Miller