“An efficient synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate: A useful intermediate in the synthesis of converting enzymeinhibitors”

✍ Scribed by Gary A. Flynn; Douglas W. Beight

• Publisher: Elsevier Science
• Year: 1988
• Tongue: French
• Weight: 171 KB
• Volume: 29
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)80112-4

✦ Synopsis

Optically pure Ethyl (R)-2-hydroxy-4-phenylbutyrate has been synthesized stereoselectively in 24% overall yield. The recent discovery of potent inhibitors of angiotensin-converting enzyme (ACE) which incorporate the ethyl N-substituted-(S)-2-amino-4-phenylbutyrate moiety as a comnon structural element' has prompted the development of varied methods for the stereoselective introduction of this residue. This goal has been successfully achieved through the reduction of Schiff-bases derived from an amine and ethyl 2-oxo-4-phenylbutyrate' and through conjugate addition of amines to ethyl 4-oxo-4-phenylcrotonate3 followed by reduction (Scheme 1). Perhaps the most stereospecific, versatile, and efficient approach, (R)-triflate & by amines. however, is the SN2 displacement of This reaction has the advantage of consistently providing the desired (S)-amino ester derivative resulting from stereospecific inversion in high yield 090%).