PROCESS FOR LARGE-SCALE SYNTHESIS OF 2', 3'-DIDEHYDRO- 3'-DEOXYTHYMIDINE (D4T) INVOLVING THE ISOLATION OF A D4T N-METHYLPYRROLIDINONE SOLVATE AND THE INTERMEDIATE D4T NMPO SOLVATE THEREFOR

摘要

An improved process for producing 2', 3'-didehydro-3'- deoxythymidine (d4T) comprising the steps of: (a) reacting thymidine (V) with mesyl chloride in the presence of an organic base selected from the group consisting of N-methyl-morpholine, the picolines, and the lutidines, to give 3', 5'-di-O- mesylthymidine (b) treatment of the bis-mesylate (IV) with aqueous hydroxide to form 3', 5'-anhydrothymidine (c) conversion of (III) into d4T NMPO solvate (II) by heating (III) in alcoholic hydroxide and, after acid neutralization, treating the reaction mixture with N-methylpyrrolidinone and an aprotic ester, amide or ketone solvent to precipitate (II); and (d) heating the isolated d4T NMPO solvate (II) in alcoholic solution to yield d4T (I) in high purity. 1603 ד' באב התשס" א - July 24, 2001 The d4T NMPO solvate of formula (II) is claimed as novel.