Beilstein J. Org. Chem.2018,14, 2340–2347, doi:10.3762/bjoc.14.209
][12][13]. In our prior publication [14], this method was selected as the technology for the development of a process to prepare (R)-(+)-1-(5’-bromopentyl)-1-methyl-7-methoxy-2-tetralone, a key intermediate of dezocine, and N-(p-trifluoromethylbenzyl)cinchonidinium bromide (3) among 17 cinchona
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Graphical Abstract
Scheme 1:
Commercial process for the synthesis of 1.
Beilstein J. Org. Chem.2018,14, 1421–1427, doi:10.3762/bjoc.14.119
10.3762/bjoc.14.119 Abstract In order to prepare asymmetrically (R)-(+)-1-(5-bromopentyl)-1-methyl-7-methoxy-2-tetralone (3a), a key intermediate of dezocine, 17 cinchona alkaloid-derived catalysts were prepared and screened for the enantioselective alkylation of 1-methyl-7-methoxy-2-tetralone with 1,5
-dibromopentane, and the best catalyst (C7) was identified. In addition, optimizations of the alkylation were carried out so that the process became practical and effective.
Keywords: alkylation; asymmetric catalysis; cinchonidine; dezocine; Introduction
The preparation of enantiomerically pure compounds has
become a stringent requirement for pharmaceutical synthesis [1]. In this context, asymmetric catalysis is probably one of the most attractive procedures for the synthesis of active pharmaceutical ingredients (APIs) due to environmental, operational, and economic benefits.
Dezocine, (5R,11S,13S)-13-amino