Merck + Co., Inc.

E.i. Dupont De Nemours and Company

Anthony O King

Richard F Shuman

Ralph P Volante

Ichiro Shinkai

Kevin M Anderson

Robert D Larsen

Sandor Karady

Ann E DeCamp

Newton L Abramson

Robert K Anderson

Thomas R Verhoeven

Alan W Douglas

Mangzhu Zhao

Sander G Mills

Leonard M Weinstock

Young S Lo

Norihiro Ikemoto

Lucius Thomas Rossano

Lelia M Fuentes

Alan T Kawaguchi

Richard E Shuman

Michael M Chartrain

A process for selectively debrominating polybromoalkyl aryl ketones and polybromoalkyl heteroaryl ketones is disclosed. The process comprises contacting an alpha-polybrominated ketone with an alkali metal sulfite in the presence of a C,-C,alkylcarboxylic acid to obtain a selectively mono-debrominated product.

Process for selective mono-debromination of polybromoalkyl aryl or heteroaryl ketones

A process for preparing cis-(1S,2R)-indanediol is disclosed. The process comprises (A) fermenting a culture medium containing a yeast strain selected from the group consisting of,MY 1506 (ATCC 74440) and mutants thereof and 1,2-indanedione to form cis-(1S,2R)-indanediol; and (B) recovering cis-(1S,2R)-indanediol from the culture medium. A process for preparing (1S)-amino-(2R)-indanol from the recovered cis-(1S,2R)-indanediol via the Ritter reaction is also disclosed.

Process for the preparation cis-(1S,2R)-indanediol by direduction of 1,2-indanedione using trichosporon cutaneum

The present invention relates to an improved process for the in situ preparation of diisopinocampheylchloroborane which comprises reacting sodium borohydride and boron trichloride with .alpha.-pinene. The diisopinocampheylchloroborane thus obtained may be used, without isolation, to reduce prochiral ketones to their corresponding alcohols in high optical purity.

Process for the preparation of diisopinocampheylchloroborane

Method for the preparing biphenyltetrazole compounds which are angiotensin II receptor antagonists or which are useful intermediates to prepare angiotensin II receptor antagonists. An illustrative biphenyl tetrazole compound is 2-n-butyl-4-chloro-1-[(2'-(tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-im idazole-5-methanol, potassium salt.

Process for preparing biphenyltetrazole compounds

A novel single-pot trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si-OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the .alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the .alpha.-methylene carbon, of .DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase.

Trialkylsilyl trifluoromethanesulfonate mediated .alpha.-methylenic

A novel, facile, and specific process for .alpha.-iodinating or .alpha.-brominating the .alpha.-methylenic carbon of a straight chain, branched chain, or cyclic secondary amide, such as a lactam or an azasteroid, comprises reacting the amide with trialkylsilyl-X (R.sub.3 Si--X), where X is Br, I, or Cl, and R is methyl, ethyl, or n-propyl, in the presence of I.sub.2 or Br.sub.2. The .alpha.-iodo- or .alpha.-bromo-amide is useful for making the .alpha.,.beta.-unsaturated amide through dehydrohalogenation.

Process for iodinating or brominating the .alpha.-methylenic carbon of a

A novel single-pot trialkylsilyl trifluoromethanesulfonate (R.sub.3 Si--OTf) mediated process produces derivatives of 4-aza 3-keto steroids at the .alpha.-methylenic carbon through electrophilic substitution. These derivatives are useful in the preparation, through elimination of the substituent on the .alpha.-methylene carbon, of .DELTA.-1 olefin 4-aza 3-keto steroids which are potent inhibitors of 5-.alpha. reductase.

There is disclosed a process for preparing the active metabolite of an angiotensin II antagonist from its pro-drug compound.

Process for preparing an angiotensin II antagonist

A multistep process is described for selectively obtaining 1-.beta.-methylcarbapenem intermediates in high overall yield. The desired 1-.beta.-methyl chirality is obtained through the hydrogenation of certain bicyclic .beta.-lactam ring structures containing an exocyclic methylene double bond alpha to the .beta.-lactam ring, in the presence of a metallic nickel hydrogenation catalyst. The hydrogenation results in a mixture of .alpha.- and .beta.-methyl isomers having a high .beta./.alpha.epimeric molar ratio. New 1-.beta.-methylcarbapenem intermediates containing the exocyclic double bond are also described.

Chiral 1-.beta.-methyl-carbapenem intermediates

A unique process for preparing certain (2R-trans)hexahydroaroquinolizines, especially (2R-trans)-N-[2-(1,3,4,6,7,12b-hexahydro-2'-oxospiro[aro-[2,3-a]-quinolizi ne-2,4'-imidazolidin]-3'-yl) ethyl)-methanesulfonamide from (2R-trans)-N-[2-[(2-cyano-(1,3,4,6,7,12b-hexahydro-aro-[2,3-a]quinolizin-2 -yl)amino]ethyl]methanesulfonamide is described.

Process for certain (2R-trans)hexahydroaroquinolizines

This invention discloses novel intermediates and novel process for their preparation where said intermediates are useful for the preparation of 5-oxygenated derivatives (T) of lovastatin and analogs thereof at the 8-acyl side chain and 6-position of the polyhydronaphthyl ring. Said derivatives of lovastatin (T) and analogs thereof are useful in treating hypercholesterolemia and are disclosed in the U.S. Pat. No. 4,963,538. ##STR1##

Processes and intermediates for the preparation of 5-oxygenated HMG-CoA

A process utilizes the tetrazole functional group to direct lithiation at the ortho position of a phenyltetrazole and generate a nucleophilic aryllithium species which then undergoes reaction with an electrophile to generate a 2-substituted 1-(tetrazol-5-yl)benzene. The process is useful in the production of intermediates in the synthesis of angiotensin II antagonists. This novel process is a more cost effective and versatile route for the large-scale preparation of these key intermediates.

Ortho-lithiation process for the synthesis of 2-substituted

A process for introducing a 1,2 double bond into a compound of the formula ##STR1## which comprises the process of (a) treating the compound of formula I with oxalyl chloride; (b) brominating the product of step (a) followed by in situ dehydrobromination; (c) deprotecting the product of step (b) to yield the .alpha. and .beta. isomers; (d) dehydrobrominating the product of step (c), which results in the introduction of a double bond at the 1,2 position.

Method for introducing a 1,2 double bond into azasteroids

A unique process for preparing certain (2R-trans)hexahydroaroquinolizines, especially (2R-trans)-N-[2-(1,3,4,6,7,12b-hexahydro-2'-oxospiro[aro-[2,3-a]-quinolizi ne-2,4'-imidazolidin]-3'-yl)ethyl)-methanesulfonamide from (2R-trans)-N-[2-[(2-cyano-(1,3,4,6,7,12b-hexahydro-aro-[2,3-a]quinolizin-2 -yl)amino]ethyl]methanesulfonamide is described.

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Hillsborough, NJ, United States of America

Anthony O King