Mallinckrodt, Inc.

The Nutrasweet Company

Joseph P Haar, Jr

Gary Lee Cantrell

Robert E Halvachs

Kevin R Roesch

Peter Xianqi Wang

Henry J Buehler

Indra Prakash

Keith G Tomazi

Brian Orr

George H Klemm

Gary A Nichols

Carl J Schaefer

Robert Y Zhao

Charles S Kuivila

An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.

Process for the preparation of quaternary N-alkyl morphinan alkaloid salts

The present disclosure generally related to an improved process for the preparation of various piperidine derivatives. More particularly, the present disclosure related to an improved process for preparing sufentanil base (1) and related compounds, which advantageously utilizes more cost effective and/or less hazardous reagents, including a dispersion comprising between about 50% and about 70% by weight (based on the total weight of the dispersion) of an alkali metal hydride, such as sodium hydride, as well as eliminates the need for expensive and/or time consuming purification techniques. 

Process for the preparation of sufentanil base and related compounds

The present invention relates to novel crystalline forms of naltrexone methobromide including hydrated and solvated forms. The invention also describes methods of preparing the various crystalline forms. The present invention also relates to pharmaceutical compositions containing crystalline forms of naltrexone methobromide, as well as methods of treating or preventing opioid induced side effects by administering the pharmaceutical compositions.

Crystalline forms of naltrexone methobromide

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.

Synthesis of methylphenidate and analogs thereof

This invention relates to the purification of N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester by resolving a mixture of the alpha- and beta-isomers of N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester using metal ions.

Metal ion assisted N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester isomer resolution

Growing community of inventors

Edwardsville, IL, United States of America

Joseph P Haar, Jr