2,2-Difluoro-2-(fluorosulfonyl)acetic acid → Ethyl 1-((difluoromethoxy)methyl)cyclobutanecarboxylate

Temperature

50 °C

To a stirred solution of ethyl 1-(hydroxymethyl)cyclobutanecarboxylate (0.2 g, 1.264 mmol) in acetonitrile (2 mL) was added CuI (0.120 g, 0.632 mmol) and the reaction mass was heated to 50° C. 2,2-Difluoro-2-(fluorosulfonyl)acetic acid (0.196 mL, 1.896 mmol) added dropwise to the solution and the reaction mixture was stirred at 50° C. for 4 h. The reaction mixture was cooled to RT and extracted with EtOAc (3×15 mL). The combined organic layer was washed with a 10% aqueous solution of NaHCO3, dried over Na2SO4, filtered and the filtrate concentrated to afford Intermediate 223A as a brown oil (0.2 g, 76%). 1H NMR (300 MHz, DMSO-d6) δ ppm 6.94-6.39 (m, 1H), 4.16-3.99 (m, 4H), 2.41-2.17 (m, 2H), 2.08-1.73 (m, 4H), 1.26-1.09 (m, 3H).

1. temperatureThe reaction mixture was cooled to RT
2. extractionextracted with EtOAc (3×15 mL)
3. washThe combined organic layer was washed with a 10% aqueous solution of NaHCO3
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated

ORD record

ord-42822d8344754ca3be083fce78d0b132

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2