Ethyl bromodifluoroacetate → HCID 57577517, compound

tert-Butyl (3-chlorophenyl)[(1S)-1-methyl-2-oxoethyl]carbamate (19.5 g) and ethyl bromodifluoroacetate (41.3 g) were dissolved in tetrahydrofuran (110 mL), and to a suspension of a zinc powder (13.6 g) in tetrahydrofuran (25 mL) was added dropwise the solution at room temperature. After heating under reflux for 1 hr, the mixture was cooled to room temperature, 1 mol/L aqueous potassium hydrogen sulfate solution (300 mL) was added, and the mixture was extracted with ethyl acetate. The extracted organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→10%), the obtained oil was dissolved in 4 mol/L hydrogen chloride/ethyl acetate solution (100 mL), and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated under reduced pressure, tetrahydrofuran (275 mL) and diisopropylethylamine (21.3 mL, 119 mmol) were added, and the mixture was heated under reflux for 12 hr. The reaction solution was cooled to room temperature, water (200 mL) was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=10→40%) to give the title compound as a yellow oil (yield: 3.76 g, 21%).

1. additionwas added dropwise the solution at room temperature
2. temperatureAfter heating
3. temperatureunder reflux for 1 hr
4. extractionthe mixture was extracted with ethyl acetate
5. washThe extracted organic layer was washed with saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=0→10%)
9. dissolutionthe obtained oil was dissolved in 4 mol/L hydrogen chloride/ethyl acetate solution (100 mL)
10. additionwere added
11. temperaturethe mixture was heated
12. temperatureunder reflux for 12 hr
13. temperatureThe reaction solution was cooled to room temperature
14. extractionthe mixture was extracted with ethyl acetate
15. washThe obtained organic layer was washed with saturated brine
16. dry with materialdried over anhydrous magnesium sulfate
17. concentrationconcentrated under reduced pressure
18. customThe residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=10→40%)

ORD record

ord-aa172154e00e4e25a6f5e86d73079687

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2