A practical synthesis of 3-ethyl-l-norvaline

An efficient process for the synthesis of 3-ethyl-l-norvaline has been developed. The route makes use of a Strecker reaction, whereby (S)-(−)-α-methylbenzylamine acts as a chiral auxiliary to provide nearly diastereomerically pure α-amino nitrile. Crystallization-induced asymmetric transformation enhances the yield and diastereomeric ratio and allows for efficient isolation of the product. The amino nitrile intermediate is converted to enantiomerically pure 3-ethyl-l-norvaline in three steps.

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3-Ethyl-l-norvalineC7H15NO2Ee = 100%[α]D25=+40 (c 0.5, 5 M HCl)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(2S)-3-Ethyl-2-{[(1S)-1-phenylethyl]amino}pentanenitrileC15H22N2Ee = 100%[α]D25=-187.4 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2S)