Ethanol → 1-Ethyl 3,3-difluoro-1,1-cyclobutanedicarboxylate

Diethyl 3,3-difluorocyclobutane-1,1-dicarboxylate (161) (2.8 g, 12 mmol) was dissolved in ice cooled ethanolic potassium hydroxide solution (0.5 M, 11 mL) and water (2.2 mL). The mixture was stirred at room temperature overnight. An additional 0.5 eq was added to the solution at room temperature and the mixture was stirred at room temperature overnight. Water was added and most of the EtOH was removed under reduced pressure. The mixture was acidified with 2M HCl and extracted three times with ethyl acetate. The organic layer was dried with magnesium sulfate and concentrated to yield 1-(ethoxycarbonyl)-3,3-difluorocyclobutanecarboxylic acid (162). 1H NMR (400 MHz, CD2Cl2) δ 4.33-4.24 (m, 2H), 3.26-3.13 (m, 4H), 1.34-1.27 (m, 3H). MS m/z 209.2 (M+1)+.

1. additionAn additional 0.5 eq was added to the solution at room temperature
2. stirringthe mixture was stirred at room temperature overnight
3. customwas removed under reduced pressure
4. extractionextracted three times with ethyl acetate
5. dry with materialThe organic layer was dried with magnesium sulfate
6. concentrationconcentrated

ORD record

ord-d7f057c27caf49dc90ab71670de6c5c5

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09199981B2