Patent ID: 8912327

Claim:
A process for producing 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-[3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine, Sitagliptin, of formula (I) comprising the following steps: a) alkylating an acyloxazolidinone of formula (II) containing an Evans' chiral auxiliary, with an alkylhaloacetate or a benzylhaloacetate of formula XCH2COOR 4 obtaining an intermediate compound (III): b) cleaving the Evans' chiral auxiliary from intermediate (III) obtaining the corresponding acid (IV): c) transforming acid (IV) into isocyanate (V), which treated with an alkylic or arylalkylic alcohol R 5 —OH leads to the formation of the corresponding carbamate (VI): d) selectively deprotecting the ester group of carbamate (VI) obtaining the corresponding acid (VII): e) condensing the thus obtained acid (VII) with the triazolpiperazine (VIII) to yield carbamate (IX): f) transforming carbamate (IX) into Sitagliptin (I): in which R 1 , R 2 and R 3 are, independently from each other, hydrogen, C1-C6 alkyl, or an aromatic or alkylaromatic group; R 4 and R 5 are alkyl or benzyl; and X is a halogen, with the provisos that: at most two of the substituents R 1 , R 2 and R 3 are simultaneously hydrogen; and when R 4 is alkyl, then R 5 is benzyl, and vice versa.