Hydrochloric Acid → 4,4-Difluoro-3-oxopentanoic acid ethyl ester

Lithium hexamethyldisilazide (150 ml of a 1M solution in THF, 0.15 mol) was cooled in an argon athmosphere to −78° C. and ethyl acetate (15 ml, 0.14 mol) was added dropwise with stirring. Stirring was continued for one hour at −78° C., then ethyl 2,2-difluoropropionate (12 g, 0.089 mol) was added dropwise with stirring. Stirring was continued for four hours at −78° C., then a saturated solution of ammonium chloride (175 ml) was added dropwise. The mixture was allowed to reach room temperature, acidified with 1M HCl (50 ml) and left standing overnight. The phases were separated. The aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with 1M HCl, brine, dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by vacuum distillation (54 mbar, 130° C.) to yield 12.4 g (0.068 mmol, 77%) of a colourless liquid that was used directly in the next step.

1. stirringStirring
2. stirringwith stirring
3. stirringStirring
4. waitwas continued for four hours at −78° C.
5. customto reach room temperature
6. waitleft
7. waitstanding overnight
8. customThe phases were separated
9. extractionThe aqueous phase was extracted with ethyl acetate
10. washthe combined organic phases were washed with 1M HCl, brine
11. dry with materialdried over sodium sulfate
12. customThe solvent was removed under reduced pressure
13. distillationthe residue was purified by vacuum distillation (54 mbar, 130° C.)

ORD record

ord-60e0ba638fe74c149298049cb03451f8

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321724B2