Pfizer Corporation

The Upjohn Co.

Pharmacia & Upjohn Company

Amphlett Greg Padilla

Bruce Allen Pearlman

Jeffrey L Havens

Haifeng Wu

Sonja S Mackey

Joel E Huber

John M Beaton

Sonja Suzanne MacKey

Max E Breuer

The present invention involves intermediates, including a 7&#x3b1;-substituted steroid (II), and processes which are used to prepare eplerenone, a useful pharmaceutical agent.

7&#x3b1;-Hydroxyacetyl and 7&#x3b1;-Hydroperoxyacetyl-substituted steroid compounds

7 &#x3b1;-Enedione-substituted steroid compounds

7&#x3b1;-biscarbonyl-substituted steroid compounds

Processes to prepare eplerenone

The present invention involves two processes for the purification of a mixture of 2,4-di(1-pyrrolidinyl)-6-chloropyrimidine (III) ##STR1## and 4,6-di(1-pyrrolidinyl)-2-chloropyrimidine (IV) ##STR2## to where &lt;1.0% of 4,6-di(1-pyrrolidinyl)-2-chloropyrimidine (IV) is present. In addition also disclosed is a process which not only purifies 2,4-di(1-pyrrolidinyl)-6-chloropyrimidine (III) but produces the commercially important 2,4-di(1-pyrrolidinyl)-6-(1-piperazinyl)pyrimidine (IX) directly.

Processes for purification of 2,4-di(1-pyrrolidinyl)-6-chloropyrimidine

Novel processes for making arylpropionic acids are described. One process comprises carboxylating particular Grignard compounds which are the products of a catalyzed reaction between corresponding arylmagnesium bromides and ethylene. Furthermore, the reaction making the particular Grignard compounds is itself novel. Also, an improved method is disclosed for making coupled aryl compounds useful as intermediates for making compounds having a pharmaceutical use. For example, particular biaryls may be used to make some of the Grignard compounds herein from which the arylpropionic acids are made. Finally, an improved bromination is disclosed giving high yields of 4-bromo-2-fluoroaniline, which is thereafter coupled with benzene, then used to make the arylmagnesium bromide reacted with ethylene to obtain the particular Grignard compound and subsequent desired arylpropionic acid, i.e. 2-(2-fluoro-4-biphenylyl)propionic acid.

Selective halogenation of 2-fluoroaniline

The present invention discloses a process for the production of androsta-4,9(11)-diene-3,17-dione type compounds from 9.alpha.-hydroxyandrostenedione type compounds by non-aromatic oxygenated strong acid dehydration.

Non-aromatic oxygenated strong acid dehydration of

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Portage, MI, United States of America

Amphlett Greg Padilla