Ethanol → Ethyl 4,4-difluoroacetoacetate

Temperature

65 °C

To a freshly prepared solution of sodium ethoxide (prepared by addition of 1.11 g, 48.35 mmol Na metal in 8 mL EtOH) in EtOH was added a solution of ethyl difluoroacetate (5.0 g, 40.29 mmol) in EtOAc (9 mL) at rt and the reaction mixture was heated at 65° C. for 2 h. Then the reaction mixture was quenched with 1N HCl at rt and the pH was adjusted to 6-7. Then the reaction mixture was extracted with EtOAc and the organic layer was washed with water and brine, separated, dried, filtered and concentrated to afford 5.5 g of ethyl 4,4-difluoro-3-oxobutanoate which was taken to the next step without further purification. To a mixture of ethyl 4,4-difluoro-3-oxobutanoate (5.5 g, 33.11 mmol) and triethyl orthoformate (12 mL, 66.26 mmol) was added acetic anhydride (27.0 g, 265.0 mmol) and the reaction mixture was heated at 100° C. for 12 h. Then the reaction mixture was concentrated to afford 5.5 g of the title product which was taken to the next step without further purification.

1. customThen the reaction mixture was quenched with 1N HCl at rt
2. extractionThen the reaction mixture was extracted with EtOAc
3. washthe organic layer was washed with water and brine
4. customseparated
5. customdried
6. filtrationfiltered
7. concentrationconcentrated

ORD record

ord-15ba452c91cd4104961f906a091b80ba

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006257B2