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R-Amino acid esters 1, 2 and 3 are novel compounds possessing hypnotic activity. On attempting an asymmetric synthesis of these molecules, racemisation was observed when reacting bis(2-methoxyethyl)amine with α-bromo intermediate 4. In vitro plasma stability studies showed that the R enantiomers had much greater resistance to esterase-mediated degradation than the corresponding S enantiomers. This observation led to the use of commercially available pig liver esterase to prepare 1, 2 and 3 on a multigram scale. The crystal structures of 1 and 2 are reported and confirm R configuration.Scheme 1 Attempted synthesis of (R)-1 and (R)-2 from (S)-2bromobutyric acid. Reagents and conditions: (i) PyBroP, DCM, i Pr 2 EtN, DMAP, 2,6-dimethoxyphenol or 2,6-dimethoxy-4-methylphenol, RT, 18 h; (ii) bis(2-methoxyethyl)amine, PhMe, 100 ЊC, 2 d.

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