Ethyl difluoroacetate → 1378683-82-9

Temperature

-78 °C

To a solution of 1-bromo-2-fluorobenzene (10.00 g, 57.14 mmol) in THF (200 mL) was added n-butyllithium (2.5 M, 24.00 mL) drop-wise at −78° C. over a period of 15 minutes under N2. The mixture was stirred at −78° C. for 30 min. Ethyl 2,2-difluoroacetate (10.64 g, 85.71 mmol) was added dropwise at −78° C. and stirred for 2 hours at −78° C. TLC showed no starting material remained. Saturated aqueous NH4Cl (15 mL) was added dropwise at −78° C. The reaction mixture was warmed to 25° C., extracted with ethyl acetate (100 mL, three times). The combined organic phases were washed with brine (30 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (petroleum ether: ethyl acetate=95:5) to afford 2,2-difluoro-1-(2-fluorophenyl)ethan-1-one (5.60 g, 47.8% yield, 85% purity). 1H NMR (CDCl3, 400 MHz): δ 7.99-7.95 (m, 1H), 7.70-7.64 (m, 1H), 7.33 (t, J=7.6 Hz 2H), 7.24 (dd, J=10.8, 8.4 Hz, 1H), 6.59-6.32 (m, 1H).

1. stirringstirred for 2 hours at −78° C
2. temperatureThe reaction mixture was warmed to 25° C.
3. extractionextracted with ethyl acetate (100 mL, three times)
4. washThe combined organic phases were washed with brine (30 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography on silica gel (petroleum ether: ethyl acetate=95:5)

ORD record

ord-e35ba9248a75434d875db041e4031d94

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346797B1