A practical and efficient protocol for the three-step synthesis of (S)-N-ethoxycarbonyl-α- methylvaline 3 is described which utilizes readily available commercial starting materials. The key transformations involve resolution-crystallization of tartrate salt 6 followed by a one- pot procedure for the preparation of 3 which is isolated as the dicyclohexylamine salt in 45% overall yield and in 91-95% ee.
