Merck + Co., Inc.

Karel M Brands

Ronald B Jobson

John M Williams

Ulf H Dolling

Ian Frank Cottrell

Michael Stewart Ashwood

Mark Cameron

Antony J Davies

Michael D Ward

Raymond Cvetovich

Louis S Crocker

Amar J Mahajan

Elizabeth S Fisher

Charles Orella

Ronald Jobson

Robert M Wenslow

Daniel R Sidler

A process of synthesizing a compound of the formula 1: ##STR1## is described. A compound of the formula 2: ##STR2## is reacted with diphenylphosphinic chloride to activate the carboxylic acid group, and then reacted with methanesulfonyl chloride to produce a compound of formula 4: ##STR3## Compound 4 is then reacted with a group II metal sulfide source in water to produce a compound of formula 1.

Process for synthesizing carbapenem side chain intermediates

Crystalline 2S-cis-3-[[(4-mercapto-2-pyrrolidinyl) carbonyl]-amino]benzoic acid and salts and solvates thereof are disclosed. Three different crystalline types are described.

Crystalline forms of antibiotic side chain intermediates

A process for the synthesis of an N-(di-substituted phosphoryl)-trans-4-hydroxy-L-proline of the formula I: ##STR1## is disclosed, wherein R.sup.1 and R.sup.2 independently represent C.sub.1-18 alkyl, phenyl or phenyl-substituted C.sub.1-18 alkyl, or R.sup.1 and R.sup.2 are taken in combination to represent C.sub.2-4 alkylidene or phenyl. Trans-4-hydroxy-L-proline is reacted with a di-(substituted) phosphite of the formula III: ##STR2## in the presence of sodium hypochlorite and sodium hydroxide to produce a compound of formula I.

A process of synthesizing a compound of the formula I: ##STR1## is described. A compound of the formula II: ##STR2## is reacted with diphenylphosphinic chloride to activate the carboxylic acid group, and then reacted with methanesulfonyl chloride to produce a compound of formula IV: ##STR3## Compound IV is then reacted with Na.sub.2 S in water to produce a compound of formula I.

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Hoboken, NJ, United States of America

Karel M Brands