Potassium Hydroxide → Stavudine

Participants

Reaction Conditions

Reaction Steps

A five liter, three-necked flask was equipped with an overhead stirrer and paddle, a reflux condenser, a temperature probe, and a heating mantle. Isopropanol (1.25 L) and potassium hydroxide (198 g, 3.0 moles) were added to the flask and heated to 50° C. stirring. Then, 3', 5'-anhydrothymidine (168.2 g, 0.75 mole) was added portion-wise. The resulting solution was then heated at 78°-80° C. for 3.5 hours. The solution was cooled to 20°-25° C., diluted with isopropanol (1.75 L), then taken to pH 4-6 with concentrated HCI and cooled to 0° C. The precipitated KCl was filtered off and washed with isopropanol (200 mL). The combined filtrate and wash was divided into three equal portions. Each portion was mixed with N-methylpyrrolidinone (54 mL) and concentrated to a thick oil at 50° C./15-20 mm Hg, then diluted with acetone (120 mL) and warmed at 50° C. for 15 minutes. The mixture was then cooled to 15° C., forming a thick slurry. The solids were collected by filtration to give a total of 65.96 g (81.6%) of the title compound which assays 68.5% (by weight) d4T.

Provenance & Evidence