Hydrochloric Acid → 3',5'-Anhydrothymidine

Participants

Reaction Conditions

Reaction Steps

A two liter, four-necked flask was equipped with an overhead stirrer and paddle, a pH probe connected to an automatic titrator, and a thermocouple probe connected to a temperature controller and a heating mantle. Water (350 mL) was added to the flask and about a 20-25% portion of 3',5'-di-O-methanesulfonylthymidine (500 g total, 1.255 moles) was added with stirring. The pH was adjusted to 10.5 with 30% aq. sodium hydroxide and the temperature was raised to 50° C. While maintaining the temperature at 50°-55° C. and the pH at 10.5-11.0, the remaining 3',5'-di-O-methanesulfonylthymidine was added slowly as material dissolved, maintaining a stirrable slurry. A total of 502 g (3.765 moles) of 30% aq. NaOH is added. The reaction mixture is then heated at 70° C. for one hour, then cooled to 10°-15° C. The pH was adjusted to 9.7-9.8 with 12N HCl using cooling to maintain the temperature at 10°-15° C. while crystallization occurred. Finally, the slurry was adjusted to pH 6.0-6.5 with 12N HCI and cooled to 0°-5° C. and filtered. The collected solids were washed with cold (0°-5° C.) water (200 mL) and air dried to give 211.6 g (75.2%) of the title compound, which assays 99.8% (by weight) purity.

Provenance & Evidence