Process for the preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine

US10829450B2 · kind B2 · utility

Assignee

• Unichem Laboratories Ltd · IN

Inventors

• Dhananjay Govind Sathe · Mumbai, IN
• Arijit Das · Margao, IN
• Yogesh Subhash Patil · Aurangabad, IN
• Nilesh L. Bonde · Salumbar, IN
• Ankush Sampat Kekan · Pune, IN

Key dates

• Filing date: Jan 11, 2018
• Grant date: Nov 10, 2020
• Expiry date: Jan 11, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D213/75
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present disclosure is related to an improved and efficient process for preparation of (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine which comprises:(a) N-acylation of 3-Amino-4-methyl pyridine; (b) Quarternization of 3-Acetylamino-4-methyl pyridine using benzyl halide; (c) Partial reduction of quarternized 3-Acetylamino-4-methyl pyridine by Sodium borohydride in Methanol or water; (d) Hydrolysis of partially reduced product to 1-Benzyl-4-methylpiperidin-3-one in presence of acid; (e) Reductive amination of 1-Benzyl-4-methylpiperidin-3-one using Methanolic methylamine in presence of Titanium(IV) isopropoxide in Methanol; (f) Resolution of 1-Benzyl-4-methylpiperidin-3-yl)-methylamine using Ditoluoyl (L) tartaric acid to get (3R,4R)-(1-benzyl-4-methylpiperidin-3-yl)-methylamine. The disclosure is also related to novel intermediates: wherein R, R′ and X are as described in the specification.