Synthesis of Trifluorothymidine: Green Glycosylation Condition Using Neither Chloroform nor Transition Metals

A new green glycosylation condition useful for efficient large-scale preparation of trifluorothymidine 1 is described. The condition requires neither CHCl3 nor transition-metal catalysts for β-selectivity at the anomeric C1-position, which is advantageous for process development of active pharmaceutical ingredients such as 1. Key features of the condition include: (1) only an equimolar amount of trifluorothymine 2 is required, (2) the glycosylation is performed under high concentration, (3) the reaction is carried out at 50 °C to enhance the reaction.