Merck + Co., Inc.

Other

Edward J Grabowski

Nobuyoshi Yasuda

Paul J Reider

Ulf H Dolling

Paul Sohar

Ann E DeCamp

Arthur A Patchett

Andrew S Thompson

Michael H Fisher

Richard D Tillyer

David J Mathre

Mark A Huffman

Thomas J Blacklock

Edward G Corley

Lyndon C Xavier

Robert F Czaja

Jan Ten Broeke

Lars M Flataker

Meyer Sletzinger

Seemon H Pines

David L Hughes

Guo-Jie Ho

Lisa F Frey

Alan W Douglas

Apurba Bhattacharya

Erwin F Schoenewaldt

John Budavari

Ulf-H Dolling

Robert D Larsen

Lushi Tan

Joseph S Amato

Richard F Shuman

Cheng Yi Chen

Todd K Jones

F Edward Roberts

Khateeta M Emerson

James J Bergan

Arthur J Zambito

Anthony M DeMarco

William F Shukis

Julie J Mohan

An efficient method for the preparation of a compound of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-ben zoxazin-2-one, also known as DMP-266, a reverse transcriptase inhibitor is achieved using a cyclization reaction of the amino alcohol intermediate with an alkyl or aryl chloroformate and a base.

Efficient synthesis of A 1,4-dihydro-2H-3,1-benzoxazin-2-one

A method of preparing intermediates for carbapenem antibiotics characterized by treating a N-deprotected acetoxy conpound of the formula: ##STR1## in the presence of a Lewis acid or a silylating agent to yeild an intermediate; and cyclizing the intermediate in the presence of rhodium (II) acetate to form a bicyclic ketoester.

Antibiotic synthesis

A process for enhancing the purity of 2R-�1-hydroxy-1-trifluoromethyl-3-cyclopropylpropyn-2-yl!-4-chloroaniline comprising the formation of an acid addition salt which is capable of rejecting the racemate in the selected organic solvent.

Process for enhancing the optical purity

An efficient method for the preparation of a compound of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl- 1,4-dihydro-2H-3, 1-benzoxazin-2-one, also known as DMP-266, a reverse transcriptase inhibitor is achieved using a cyclization reaction of the amino alcohol intermediate with an alkyl or aryl chloroformate and a base.

Efficient synthesis of a 1,4-dihydro2H-3,1-benzoxazin-2-one

An improved synthesis of a highly potent HIV reverse transcription inhibitor is disclosed, involving an acetylide and a trifluoromethyl ketone which produces a chiral product in the presence of a chiral amino alcohol.

Asymmetric synthesis of

Process to derivatives of piperizinylcamphorsulfonyl oxytocin antagonists

The present invention is directed to a compound represented by the structural formula: ##STR1## wherein Z-- represents a negatively charged counterion.

Boronic acid compound

A chiral resolution process is described for the purification of a substituted chiral quinazoline, by salt formation with a resolving agent, followed by crystallization.

Chiral resolution process

The present invention is directed to a process of making 2-aryl carbapenems of formula 1 from a compound of formula A. ##STR1## wherein compound A is reacted with a silyl protected boronic acid compound of the formula B: ##STR2## and wherein Ar is selected from the group consisting of: ##STR3##

Preparation of 2-aryl carbapenems

An asymmetric synthesis of (S)-(-)-6-chloro-4-cyclopropyl-3,4-dihydro-4-[(2-pyridyl)ethynyl]-2(1H)-qu inazolinone comprises the chiral addition of 2-pyridylacetylide to N.sup.1 -protected 6-chloro-4-cyclopropyl-2-quinazolinone followed by removal of the protecting group.

Asymmetric synthesis of (S)-(-)-6-chloro-4-

Described is a process for converting an alcohol to an azide with S.sub.N 2 inversion using a phosphoryl azide, e.g. diphenylphosphoryl azide (DPPA). Good yields of azide in high enantiomeric excess can be achieved specifically for benzylic alcohols and alpha-hydroxy alkyl esters. The process is carried at preferably room temperature in an inert dry aprotic solvent, e.g. toluene, and in the presence of a proton acceptor, e.g. 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to afford high yields of high enantiomeric purities.

Converting an alcohol to an azide with S.sub.N 2 inversion using a

5,6-Dihydro-4-(R-amino)-4H-thieno[2,3-b]-thiopyran-2-sulfonamide-7,7-dioxid e is a potent carbonic anhydrase inhibitor useful in the treatment of ocular hypertension and glaucoma. The S-(+)-enantiomer of that compound, the more active enantiomer, is prepared by a process involving an intermediate step of an enantioselective reduction of a carbonyl group employing an oxazaborolidine chiral catalyst.

Enantiospecific synthesis of

A process for dehydrogenating a compound of the formula ##STR1## which comprises reacting the compound with a silylating agent in the presence of a quinone to introduce a .DELTA..sup.1 double bond.

Dehydrogenation process intermediates

A process is disclosed for obtaining manipulated proportions of the (+) and (-) enantiomers of [(6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-2-phenyl-1H-inden-5-yl)oxy]aceti c acid by asymmetric chiral phase transfer catalysis.

Trifluoromethylbenzyl containing quaternary salts

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Westfield, NJ, United States of America

Edward J Grabowski