Hydrochloric Acid → HCID 54189546, compound

Temperature

0 °C

Potassium 3-(ethyoxy)-3-oxopropanoate (1.97 g, 11.6 mmol, 2.1 equiv) was suspended in acetonitrile (15 mL), cooled to 0° C. and treated with successively with triethylamine (2.46 mL, 17.7 mmol, 3.2 equiv) and magnesium(II) chloride (1.31 g, 13.8 mmol, 2.5 equiv). The ice bath was removed and the mixture was warmed to ambient temperature and stirred for an additional for 2.5 hours. An acetonitrile solution (5 mL) of 3-chlorothiophene-2-carbonyl chloride (1.00 g, 5.52 mmol) was added and the mixture was stirred for 72 hours at ambient temperature. The mixture was concentrated in vacuo and the residue was concentrated from toluene (1×75 mL), providing a white solid. The solid was suspended in toluene (˜50 mL), cooled to 0° C. and treated with hydrochloric acid (˜20 mL, 12 N aqueous) with vigorous stirring. After 15 minutes, the ice bath was removed and the mixture was warmed to ambient temperature and stirred for 45 minutes. The mixture was poured into water (50 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 75:25; hexanes:ethyl acetate), providing the titled compound.

1. customThe ice bath was removed
2. temperaturethe mixture was warmed to ambient temperature
3. stirringthe mixture was stirred for 72 hours at ambient temperature
4. concentrationThe mixture was concentrated in vacuo
5. concentrationthe residue was concentrated from toluene (1×75 mL)
6. customproviding a white solid
7. temperaturecooled to 0° C.
8. waitAfter 15 minutes
9. customthe ice bath was removed
10. temperaturethe mixture was warmed to ambient temperature
11. stirringstirred for 45 minutes
12. additionThe mixture was poured into water (50 mL)
13. extractionextracted with ethyl acetate (3×75 mL)
14. dry with materialThe combined organic extracts were dried with sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated in vacuo
17. customThe residue was purified by silica gel gradient chromatography (100:0 to 75:25; hexanes:ethyl acetate)

ORD record

ord-4c3786ea06e047d08ff582be9e131587

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293744B2