Ethyl chloroformate → HCID 178437954, compound

Ethylchloroformate (0.30 ml, 3.08 mmol) was added to a stirred solution of the amidoxime of Example 8 (500 mg, 1.39 mmol) in pyridine (8 ml) at 0° C. under nitrogen and the resulting solution was stirred for 10 minutes. The mixture was concentrated under reduced pressure and the residue was dissolved in a mixture of water (4 ml), tetrahydrofuran (4 ml) and 1M aqueous sodium hydroxide solution (2 ml). The mixture was heated under reflux for 1 hour, cooled to room temperature and stirred for a further 2 days. The resulting solution was diluted with 2M aqueous hydrochloric acid (20 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with brine (50 ml), dried over magnesium sulphate, filtered and evaporated under reduced pressure to leave a yellow oil. The oil was purified by flash column chromatography on silica gel eluting with pentane:ethyl acetate (50:50, by volume) to yield a white solid. The solid was dissolved in a mixture of tetrahydrofuran (1 ml) and 1M aqueous sodium hydroxide solution (10 ml) and then heated under reflux for 24 hours. The resulting solution was diluted with 2M hydrochloric acid (20 ml) and extracted with dichloromethane (2×50 ml). The combined organic layers were washed with brine (50 ml), dried over magnesium sulphate, filtered and evaporated under reduced pressure to give the title compound (113 mg) as a white solid m.p. 94-96° C.

1. concentrationThe mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in a mixture of water (4 ml), tetrahydrofuran (4 ml) and 1M aqueous sodium hydroxide solution (2 ml)
3. temperatureThe mixture was heated
4. temperatureunder reflux for 1 hour
5. stirringstirred for a further 2 days
6. additionThe resulting solution was diluted with 2M aqueous hydrochloric acid (20 ml)
7. extractionextracted with ethyl acetate (2×50 ml)
8. washThe combined organic layers were washed with brine (50 ml)
9. dry with materialdried over magnesium sulphate
10. filtrationfiltered
11. customevaporated under reduced pressure
12. customto leave a yellow oil
13. customThe oil was purified by flash column chromatography on silica gel eluting with pentane:ethyl acetate (50:50, by volume)
14. customto yield a white solid
15. temperatureheated
16. temperatureunder reflux for 24 hours
17. extractionextracted with dichloromethane (2×50 ml)
18. washThe combined organic layers were washed with brine (50 ml)
19. dry with materialdried over magnesium sulphate
20. filtrationfiltered
21. customevaporated under reduced pressure

ORD record

ord-91d62b60b2d84710974fd578ea4a84b7

Source dataset

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08063044B2