Triethylamine → Ethyl 3-[2-fluoro-6-(methyloxy)phenyl]-3-oxopropanoate

Temperature

5 °C

Potassium ethylmalonate (2.1 g, 12 mmol, 2.1 equiv) was suspended in acetonitrile (20 mL), cooled to 5° C. and treated with successively with triethylamine (2.6 mL, 18 mmol, 3.2 equiv) and magnesium(II) chloride (1.4 g, 14 mmol, 2.5 equiv). The ice bath was removed and the mixture was warmed and stirred at ambient temperature for 2.5 hours. An acetonitrile solution (5 mL) of 2-fluoro-6-(methyloxy)benzoyl chloride (1.1 g, 5.8 mmol) was added and the mixture was stirred for 2 hours at ambient temperature. The mixture was concentrated in vacuo and the residue was suspended in toluene (50 mL), cooled to 0° C. and treated with hydrochloric acid (20 mL, 12 N aqueous) with vigorous stirring. The ice bath was removed after 10 minutes and the mixture was warmed to ambient temperature and stirred for an additional 15 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 1:1; hexanes:ethyl acetate), providing the titled compound.

1. customThe ice bath was removed
2. temperaturethe mixture was warmed
3. stirringthe mixture was stirred for 2 hours at ambient temperature
4. concentrationThe mixture was concentrated in vacuo
5. temperaturecooled to 0° C.
6. additiontreated with hydrochloric acid (20 mL, 12 N aqueous) with vigorous stirring
7. customThe ice bath was removed after 10 minutes
8. temperaturethe mixture was warmed to ambient temperature
9. stirringstirred for an additional 15 minutes
10. additionThe mixture was poured into water (50 mL)
11. extractionextracted with ethyl acetate (3×75 mL)
12. dry with materialThe combined organic extracts were dried with sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe residue was purified by silica gel gradient chromatography (100:0 to 1:1; hexanes:ethyl acetate)

ORD record

ord-67ac534b41014b92982e01bd2398f5c2

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895580B2