Mallinckrodt, Inc.

Charles S Kuivila

Joseph P Haar, Jr

Carl J Schaefer

A synthetic process for the preparation of amino acid esters such as methylphenidate and analogs thereof is disclosed. The process involves reacting an amino acid such as &#x3b1;-phenyl-&#x3b1;-(2-piperidinyl)acetic acid or an analog thereof with an alcohol such as methanol in the presence of an acid and a water sequestrant such as trimethyl orthoacetate. In some embodiments, the water sequestrant is added to the reaction mixture after an initial period of esterification and then the reaction is allowed to continue. The &#x3b1;-phenyl-&#x3b1;-(2-piperidinyl)acetic acid methyl ester or analog thereof is then isolated from the reaction mixture. In one variation of the process, the supernatant liquid may be recycled in subsequent runs to increase yield and product purity.

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St. Louis, MO, United States of America

Charles S Kuivila