PROCESS FOR PREPARING OF 2'-DEOXY-2'2'-DIFLUOROCYTIDINE

摘要

PURPOSE: A method for preparing 2'-deoxy-2',2'-difluorocytidine is provided to obtain useful compound in manufacturing gemcitabine with high yield and high purity. CONSTITUTION: A method for preparing 2'-deoxy-2'2'-difluorocytidine of chemical formula 1 and salt thereof comprises: a step of reacting ethyl 3-hydroxy propanic acid ester compound of chemical formula 9 with optically pure amine-based compound to obtain 3R-hydroxy propane amide compound of chemical formula 8; a step of protecting hydroxyl group of the compound of chemical formula 8 to obtain a compound of chemical formula 7; a step of hydrolyzing the compound of chemical formula 7 to D-etythro-1-oxoriboxe compound of chemical formula 6; a step of protecting hydroxyl group of the D-erythro-1-oxoribose 5th site to obtain a d-erythro-1-oxoribose compound of chemical formula 5; a step of reducing the D-erythro-1-oxoribose compound of chemical formula 5 to obtain a lactol compound of chemical formula 4; a step of reacting the lactol compound of chemical formula 4 with methansulfonyl chloride to obtain D-erythro-1-methansulfonyloxyribopurnose derivative of chemical formula 3; a step of mixing the compound of chemical formula 3 and nucleo base in organic solvent to obtain nucleoside of chemical formula 2; and a step of deprotecting the nucleoside of chemical formula 2.