Hydrochloric Acid → HCID 54535348, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of (R)-3-(5-acetoxyhexyl)-6-amino-1-methyl-5-nitroso-uracil (prepared as described for CT12452) (23.35 g, 74.8 mmol) in water (230 ml) at 60° C. was added sodium hydrosulfide (61.7 g) in portions. After heating at 60° C. for additional 1 hour, the reaction mixture was cooled to 0-5° C. Chloroform (240 ml) was added followed by potassium carbonate (51.8 g), 37.5 mmol) in portions. The reaction mixture was stirred at 0-5° C. for additional 0.5 hour whereupon benzyloxyacetyl chloride (20.7 g, 112 mmol) was added dropwise. After stirring at 0-5° C. for an additional 1 hour, the mixture was extracted with 10% methanol-chloroform solution (1100 ml). The aqueous phase was further extracted with 10% methanol-chloroform solution (3×250 ml). The combined organic extracts were evaporated under reduced pressure to provide a beige solid which was dissolved in 10% aqueous sodium hydroxide solution (500 ml) and heated at reflux for 0.5 hour. After cooling to 0-5° C., the pH was adjusted to 2-3 by addition of concentrated hydrochloric acid and the mixture was extracted with ethyl acetate (5×250 ml). The combined extracts were washed with saturated aqueous sodium chloride solution (100 ml), dried over magnesium sulfate, and concentrated under reduced pressure to provide a crude product. Recrystallization (ethyl acetate-hexane) provided (R)-8-benzyloxymethyl-1-(5-hydroxyhexyl)-3-methylxanthine (22.0 g, 77% yield) as a white solid.

Provenance & Evidence