Hydrochloric Acid → HCID 58742350, compound

Temperature

0 °C

A solution of the compound of Example 102 (80 mg, 0.23 mmol) in acetone (15 mL) was cooled to 0° C. p-Nitrobenzoyl chloride (46 mg, 0.25 mmol) and aqueous 1N sodium hydroxide solution were then added. After the mixture was stirred at 0° C. for 1.5 hours, aqueous saturated sodium bicarbonate solution was added. The mixture was extracted with ethyl acetate and the organic layer was washed with brine, dried over magnesium sulfate and concentrated to afford the crude p-nitrobenzoyl ester derivative. This was dissolved in dichloromethane (15 mL) and treated with aqueous 6N hydrochloric acid solution (0.038 mL). After it was cooled to −30° C., ozone was bubbled through the solution until disappearance of starting material was evident by thin layer chromatography. Oxygen was bubbled for an additional 5 minutes and then dimethylsulfide (0.5 mL) was added. The mixture was allowed to warm to room temperature overnight and was then concentrated. The residue was taken up in tetrahydrofuran (10 mL), treated with aqueous 1N sodium hydroxide solution (5 mL) and stirred at room temperature for 2 hours. Excess aqueous IN hydrochloric acid solution was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated aqueous sodium bicarbonate solution and brine. After drying over magnesium sulfate, evaporation provided a residue from which the title compound was isolated by chromatography on silica gel eluting with 40% ethyl acetate in hexane. Mass spectrum (m/e) 368 (M++1).

1. additionwere then added
2. extractionThe mixture was extracted with ethyl acetate
3. washthe organic layer was washed with brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. customto afford the crude p-nitrobenzoyl ester derivative
7. temperatureAfter it was cooled to −30° C.
8. customozone was bubbled through the solution until disappearance of starting material
9. customOxygen was bubbled for an additional 5 minutes
10. additiondimethylsulfide (0.5 mL) was added
11. temperatureto warm to room temperature overnight
12. concentrationwas then concentrated
13. additiontreated with aqueous 1N sodium hydroxide solution (5 mL)
14. stirringstirred at room temperature for 2 hours
15. additionExcess aqueous IN hydrochloric acid solution was added
16. extractionthe mixture was extracted with ethyl acetate
17. washThe organic phase was washed with saturated aqueous sodium bicarbonate solution and brine
18. dry with materialAfter drying over magnesium sulfate, evaporation

ORD record

ord-115d6385371741fcbe69e4fb1595a129

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07553877B2