Diastereoselective process leading to a key intermediate for the preparation of fluorinated reverse transcriptase inhibitors

US5498719A · kind A · utility

Assignee

• The United States of America as Represented by the Secretary of the Department of Health and Human Services · US

Inventors

• Victor E. Marquez · Gaithersburg, US
• John S. Driscoll · Rockville, US
• Magbool A. Siddiqui · Gaithersburg, US

Key dates

• Filing date: Jan 31, 1994
• Grant date: Mar 12, 1996
• Expiry date: Jan 31, 2014

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D317/30
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention provides a novel synthetic route to a key precursor, i.e., an (S,S)-.alpha.-fluoro-2,2-dimethyl-1,3-dioxolane-4-propanoic acid ester useful in the preparation of FddA and FddC. The instant diastereoselective process utilizes a novel intermediate which contains a chiral auxiliary. The chiral auxiliary can be any chiral auxiliary moiety such as for example an auxiliary containing a substituted oxazolidinone group. The intermediate containing the chiral auxiliary is fluorinated utilizing a fluorination method applied for the first time in the synthesis of fluorinated sugars to give a fluorinated intermediate which after removal of the chiral group provides the desired key intermediate. In summary, in the instant process, a fluorine is introduced diastereoselectively into an intermediate via the reaction of a chiral enolate with an electrophilic fluorinating agent and the intermediate which is fluorinated is derived from mannitol.