期刊
ORGANIC PROCESS RESEARCH & DEVELOPMENT
卷 16, 期 4, 页码 704-709出版社
AMER CHEMICAL SOC
DOI: 10.1021/op300012d
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In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evolution of the synthetic strategy based on the early discovery route was described. By focusing on the use of readily available starting materials it was possible to avoid chromatography steps and expensive reagents, bringing about significant improvements in cost and throughput. The best route involves construction of the chiral centre by asymmetric hydrogenation.
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