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Synthesis of a conformationally restricted analog of pregabalin by stereoselective alkylation of a chiral pyrrolidin-2-one

✍ Scribed by Roberta Galeazzi; Gianluca Martelli; Giovanna Mobbili; Mario Orena; Samuele Rinaldi

Publisher
Elsevier Science
Year
2003
Tongue
English
Weight
140 KB
Volume
14
Category
Article
ISSN
0957-4166

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✦ Synopsis

The 4-benzyloxymethyl pyrrolidin-2-one, 5, was alkylated leading to 3,4-trans-disubstituted pyrrolidin-2-one 6 in good yield and total diastereoselection, as shown by 1 H NMR data and NOE experiments. After reduction of the carbonyl group to give the trans-3,4-disubstituted pyrrolidine 7, and removal of the chiral auxiliary, followed by protection of the nitrogen with t-Boc group, the corresponding N-protected pyrrolidine, 8 was obtained. The cleavage of the benzyl ether moiety, followed by oxidation of the hydroxy function, gave in good yield the corresponding pyrrolidine carboxylic acid 2, a restricted analog of pregabalin.

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