E. R. Squibb Sons, Inc.

Fmc Corporation

Thomas C Sedergran

Richard H Mueller

Jollie D Godfrey, Jr

Nachimuthu Soundararajan

Leland A Smeltz

Carl F Anderson

Harold C Jarrow

A process for the preparation of a sulfonamide of formula (II), comprising reacting at elevated temperature an aniline of formula (I), with a sulfonating agent A of the formula R&#x2014;SO-Z in the presence of a catalytic amount of either: (i) an amide B-1, other than N,N-dimethylformamide, or (ii) a high boiling tertiary amine B-2. Also provided in accordance with the present invention are processes for preparing sulfonamides of formula (II) by reacting an aniline of formula (I) with sulfanating agent A of the formula R&#x2014;SO-Z in the presence of N,N-dimethylformamide, at a temperature in the range of about 120&#xb0; C. to about 160&#xb0; C. for about three to about seven hours. X, Y, Z, R and Rare defined herein 

Process to prepare sulfonamides

A process for preparing compounds of the formula ##STR1## where a, b, c, R.sub.1, R.sub.2, and R.sub.3 are as defined herein including the step of alkylating a phenol of formula ##STR2## with an acetylene of formula ##STR3## where X is chlorine; bromine; --OC(O)--R.sub.5, where R.sub.5 is alkyl, aryl or substituted aryl; or --OCO.sub.2 R.sub.6, where R.sub.6 is alkyl or ##STR4## in the presence of a catalytic amount of a cuprous or cupric salt. The compounds of formula I are intermediates useful in the preparation of pyranyl cyanoguanidine derivatives.

Process for the preparation of intermediates useful in the preparation

An increase in the disastereoselectivity resulting from the reaction of a phosphinic acid ester of the formula ##STR1## with the halo ester of the formula ##STR2## is achieved by carrying out the reaction in the presence of 4-methylmorpholine, diazabicyclooctane, quinuclidine, 1-methylpyrolidine, or cinchonidine. After removal of the R.sub.3 protecting group and fractional crystallization, the resulting desired diastereomeric pair can be resolved, and the desired isomer can be coupled to 4-substituted L-proline to give compounds possessing angiotensin converting enzyme inhibition activity. In particular, the process is useful in producing the antihypertensive agent fosinopril sodium in increased yields.

Diastereoselective preparation of phosphinate esters

The presence of a copper salt during the oximation of a .beta.-lactam containing compound having glyoxylamino substituents of the formula ##STR1## by reaction with an aminooxy compound having the formula

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Englishtown, NJ, United States of America

Thomas C Sedergran