Process for production of piperidine derivatives

US8022220B2 · kind B2 · utility

Assignee

• ALBANY MOLECULAR RESEARCH, INC. · US

Inventors

• Thomas E. D'Ambra · Wynantskill, US
• Garry M. Pilling · East Nassau, US

Key dates

• Filing date: Jun 11, 2009
• Grant date: Sep 20, 2011
• Expiry date: Jun 11, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D261/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention discloses a process for preparing the piperidine derivative compound 4-[4-[4-hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetic acid of formulacomprising the sequential steps of: (1) reacting 4-bromo-α,α-dimethyl-α-(4,4-dimethylisoxazolin-2-yl)toluene with 4-chlorobutyryl chloride to provide 4-(4-chloro-1-oxobutyl)-α,α-dimethyl-α-(4,4-dimethylisoxazolin-2-yl)toluene; (2) hydrolyzing said 4-(4-chloro-1-oxobutyl)-α,α-dimethyl-α-(4,4-dimethylisoxazolin-2-yl)toluene to provide 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetic acid; (3) reacting said 4-(4-chloro-1 -oxobutyl)-α,α-dimethylphenylacetic acid with methanol to provide methyl 4-(4-chloro-1 -oxobutyl)-α,α-dimethylphenylacetate; (4) reacting said methyl 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetate with 4-(α,α-diphenyl)piperidinemethanol to provide methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate; (5) reducing said methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate to provide methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetate; and (6) hydrolyzing sai…