Asymmetric synthesis of esomeprazole

A highly efficient synthesis of esomeprazole-the (S)-enantiomer of omeprazole-via asymmetric oxidation of prochiral sulphide 1 is described. The asymmetric oxidation was achieved by titanium-mediated oxidation with cumene hydroperoxide (CHP) in the presence of (S,S)-diethyl tartrate [(S,S)-DET]. The enantioselectivity was provided by preparing the titanium complex in the presence of 1 at an elevated temperature and/or during a prolonged preparation time and by performing the oxidation of 1 in the presence of an amine. An enantioselectivity of >94% ee was obtained using this method. (C) 2000 Elsevier Science Ltd. All rights reserved.