Greatly Simplified Procedures for the Synthesis of α-Amino Acids by the Direct Alkylation of Pseudoephedrine Glycinamide Hydrate

A modified procedure for the synthesis of highly enantiomerically enriched α-amino acids is described that involves the direct alkylation of pseudoephedrine glycinamide hydrate (1·H2O) followed by hydrolysis. The modified procedure was developed to overcome several inconvenient aspects of our earlie...

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Bibliographic Details
Published in:Journal of organic chemistry 1999-04, Vol.64 (9), p.3322-3327
Main Authors: Myers, Andrew G, Schnider, Patrick, Kwon, Soojin, Kung, Daniel W
Format: Article
Language:English
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Summary:A modified procedure for the synthesis of highly enantiomerically enriched α-amino acids is described that involves the direct alkylation of pseudoephedrine glycinamide hydrate (1·H2O) followed by hydrolysis. The modified procedure was developed to overcome several inconvenient aspects of our earlier reported procedure. Advantages of the new method include (1) a greatly simplified one-step synthesis of the alkylation substrate (1·H2O) by the direct combination of glycine methyl ester hydrochloride with pseudoephedrine in the presence of lithium tert-butoxide, (2) the use of the weaker base lithium hexamethyldisilazide (LHMDS) in lieu of lithium diisopropylamide (LDA) for the enolization reaction, (3) a protocol for the direct alkylation of 1·H2O without the need for prior drying of the alkylation substrate, and (4) a one-step alkylation procedure that generates LHMDS and anhydrous lithium chloride simultaneously from the reaction of lithium metal with n-hexyl chloride in the presence of hexamethyldisilazane.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo990341z