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Synthesis 2009(19): 3227-3232  
DOI: 10.1055/s-0029-1216943
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Method for the Preparation of Versatile Building Blocks: 1-Substituted 2,2-Dimethoxyethylamine Hydrochlorides

Bo Liu, Deyong Su, Guolin Cheng, Hui Liu, Xinyan Wang*, Yuefei Hu*
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
Fax: +86(10)62771149; e-Mail: wangxinyan@mail.tsinghua.edu.cn; e-Mail: yfh@mail.tsinghua.edu.cn;
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Publication History

Received 30 April 2009
Publication Date:
21 August 2009 (online)

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Abstract

A novel method for the preparation of 1-substituted 2,2-dimethoxyethylamine hydrochlorides was developed. The method includes three highly efficient steps: (1) direct use of aqueous (MeO)2CHCHO for the preparation of N,O-acetal by condensation with Betti base without acidic catalyst; (2) regioselective alkylations of the N,O-acetal with Grignard reagents; and (3) Pd/C catalytic hydrogenolyses of benzylamines in the presence of ClCH2CHCl2 to directly give the target products as crystalline amine hydrochlorides. The method reported is extremely convenient and highly efficient with wide substrate scopes.

Key words

heterocycles - alkylation - N-debenzylation - Betti base - 2,2-dimethoxyethylamines

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