Hydrochloric Acid → HCID 54535348, compound

Temperature

60 °C

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.

1. temperaturethe reaction mixture was cooled to 0-5° C
2. additionwas added dropwise
3. extractionthe mixture was extracted with 10% methanol-chloroform solution (1100 ml)
4. extractionThe aqueous phase was further extracted with 10% methanol-chloroform solution (3×250 ml)
5. customThe combined organic extracts were evaporated under reduced pressure
6. customto provide a beige solid which
7. temperatureheated
8. temperatureat reflux for 0.5 hour
9. temperatureAfter cooling to 0-5° C.
10. extractionthe mixture was extracted with ethyl acetate (5×250 ml)
11. washThe combined extracts were washed with saturated aqueous sodium chloride solution (100 ml)
12. dry with materialdried over magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. customto provide a crude product
15. customRecrystallization (ethyl acetate-hexane)

ORD record

ord-76143ae28d214718a82120fab64cd28e

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06878715B1