The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Sep. 15, 1998
Filed:
Apr. 14, 1998
Peter J Harrington, Louisville, CO (US);
Michael P Fleming, Longmont, CO (US);
Roche Colorado Corporation, Boulder, CO (US);
Abstract
A method of preparing 2-�2-{�3-(1H-benzimidazol-2-yl)propyl!methylamino)}ethyl!-6-fluoro-1-isopr opyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate comprises contacting 6-fluoro-1-isopropyl-3,4-dihydro-1H-naphthalen-2-one with the dianion of N-�3-(1H-benzimidazol-2-yl)propyl!-N-methylacetamide to form N-�3-(1H-benzimidazol-2-yl)propyl!-2-(6-fluoro-2-hydroxy-1-isopropyl-1,2,3 ,4-tetrahydronaphthalen-2-yl)-N-methylacetamide, reducing this to 2-�2-{�3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-ol, and treating the 2-�2-{�3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopro pyl-1,2,3,4-tetrahydronaphthalen-2-ol with methoxyacetic acid or an activated derivative of methoxyacetic acid. The invention is particularly applicable to the preparation of mibefradil, (lS,2S)-2-�2-{�3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro- 1-isopropyl-1,2,3,4-tetrahydronaphthalen-2-yl methoxyacetate, and its dihydrochloride salt. N-�3-(1H-Benzimidazol-2-yl)propyl!-N-methylacetamide, and the acetic acid solvate of 2-�2- {�3-(1H-benzimidazol-2-yl)propyl!methylamino}ethyl!-6-fluoro-1-isopropyl-1 ,2,3,4-tetrahydronaphthalen-2-ol dioxalate, are new.