Preparative resolutions of an α-methyl carboxylic acid through selective transformations of readily epimerizable intermediates
✍ Scribed by Kurt A. Josef; Thomas E. D'Ambra; David Rosi; Richard E. Philion
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 563 KB
- Volume
- 2
- Category
- Article
- ISSN
- 0899-0042
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✦ Synopsis
Two preparations of the enantiomers of 2 are described. The first makes use of the chromatographic separation of the diastereomeric amides 6a and 6b. Standard hydrolysis of these amides caused racemization, so a milder sequence was developed which utilized carbonyldiimidazole and 1 equivalent of 1 N LiOH.
The second preparation involved classical resolution of 9 with (bcinchonidine.
Subsequent transformations of this substrate involved ester formation, Friedel-Crafts acylation, and ester hydrolysis, all without racemization. The most notable of these reactions was the use of EtAlCl, in the Friedel-Crafts step, which provided a mild acylation of 10. This second preparation affords a high yield, mild process for the potential preparation of kilogram quantities of (-)-(R)-2b.