Hoffmann-la Roche Inc.

Roche Vitamins Inc.

Joachim Veits

Rainer Eugen Martin

Michelangelo Scalone

Andreas Zogg

Juergen Fleckenstein

Bernd Kraemer

Michael Meade

Joaquim Pintao

Walter Deichtmann

Juergen Schaefer

Dennis Smith

John Hayes

Andreas Staempfli

Christian Lautz

Leo Clarke

Christian Walch

Beat Birrer

Julius Jeisy

Andrew Walsh

A process for the preparation of a compound of formula (I): which is useful as an intermediate in the preparation of pharmaceutically active compounds.

Process for the preparation of cyclohexanecarboxylic acid derivatives

The present invention is directed to a process for the production of 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid and of 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid anhydride, starting from meso-2,3-bis(benzylamino)succinic acid dialkali metal salt. The process involves reacting meso-2,3-bis(benzylamino)succinic acid dialkali metal salt with phenyl chloroformate in a monophasic solvent system consisting of an about 2:1 to 1:1 mixture of a water-miscible ether and an aqueous alkali metal hydroxide solution, at a temperature not exceeding about 40&deg; C. The resulting 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid dialkali metal salt is converted, by acidification, into the desired 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid, which is then either isolated, or converted, by heating with acetic anhydride, in an aromatic hydrocarbon as the organic solvent, into the desired 2-oxo-1,3-dibenzyl-cis-4,5-imidazolidinedicarboxylic acid anhydride, which is in turn, isolated. Each product is an important intermediate in the multi-stage process for the manufacture of biotin (vitamin H).

Process for preparing biotin

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Florence, SC, United States of America

Joachim Veits