Crystalline forms of carbapenem antibiotics and methods of preparation

USRE40794E1 · kind E1 · reissue

Assignee

• MERCK & CO., INC. · US

Inventors

• Karel Marie Joseph Brands · Rahway, US
• Raymond Cvetovich · Scotch Plains, US
• Louis Crocker · Montgomery, US
• Michael D. Ward · McHenry, US
• Amar J. Mahajan · Piscataway, US
• Robert Wenslow · Plainsboro, US
• John M. Williams · Willow View Lane, US
• Daniel R. Sidler · Whitehouse Station, US
• Charles Orella · Clonmel, IE
• Elizabeth S. Fisher · Cranbury, US
• Ronald B. Jobson · East Brunswick Township, US

Key dates

• Filing date: Sep 20, 2002
• Grant date: Jun 23, 2009
• Expiry date: Sep 20, 2022

Classification

• Technology area (CPC —): General

Abstract

A process for preparing a crystalline, carbapenem monosodium salt of formula IIa: characterized by the steps a) adding about 10 to 30% of an organic solvent to an aqueous solution of the carbapenem, b) cooling the resulting solution to less than −5° C., c) adjusting the pH using a solution containing an acid in an organic solvent to give the appropriate pH for crystallization, and d) crystallizing the compound by adding methanol, and a C2-5 alcohol at between −5 and −25° C.