Patent ID: 8796471

Claim:
Process for the preparation of proline derivatives of formula I wherein, R 1 is selected from C 1-7 -alkyl or from wherein R 4 is selected from C 1-7 -alkyl, halogen-C 1-7 -alkyl or from phenyl which is optionally substituted by halogen; R 2 is selected from halogen or halogen-C 1-7 -alkyl; and R 3 is selected from hydrogen, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy or from a 5- or 6-membered heterocyclic ring containing one or two nitrogen atoms, the ring which is optionally substituted by C 1-7 -alkyl or halogen; comprising the steps a) transforming an alcohol of formula II wherein R 1 has the meaning as above with a sulfonating agent in the presence of an organic solvent at a temperature of −10° C. to 40° C. into the sulfonate of the formula III wherein R 1 has the meaning as above and R 5 is C 1-7 -alkyl, halogen-C 1-7 -alkyl or phenyl which is optionally substituted by C 1-7 -alkyl, nitro or bromo b) reacting the sulfonate of formula III with a thio compound of formula IV wherein R 2 and R 3 are as outlined above and R 6 is hydrogen or a protecting group in the presence of lithium-, sodium- or potassium tert-butylate in an organic solvent at temperatures between 10° C. and 90° C. to form the thioether of the formula V wherein R 1 , R 2 and R 3 are as outlined above and c) oxidizing the thioether of formula V with an oxidating agent selected from peroxymonosulfate or magnesium monoperoxyphthalate hexahydrate in the presence of an organic solvent at temperature between 0° C. and 60° C. to form the proline derivative of formula I wherein R 1 , R 2 and R 3 are as outlined above and wherein the process is further characterized in that the alcohol of formula II is prepared by a1) reacting a hydroxy proline ester of formula VI wherein R 7 is C 1-7 -alkyl with a carbonyl compound of formula VII R 1 COY VII wherein R 1 is as above and Y is halogen or OH to form a carbonyl proline ester of formula IX wherein R 1 and R 7 are as above; b1) subsequent forming of a sulfonate of formula X wherein R 1 and R 7 are as above and R 8 is C 1-7 -alkyl optionally substituted by halogen or phenyl which is optionally substituted by C 1-7 -alkyl, nitro or bromo and c1) converting the sulfonate of formula X in the presence of an amino cyclopropane carbonitrile of formula XI into the alcohol of formula II.