Water → 1-((Difluoromethoxy)methyl)cyclobutanecarboxylic acid

To a stirred solution of Intermediate 223A (0.263 g, 1.263 mmol) in ethanol (3.5 mL), THF (3.5 mL), and water (3 mL) was added NaOH (0.152 g, 3.79 mmol) and the reaction mixture was stirred at RT for 16 h. The reaction mixture was concentrated and the residue dissolved in water and extracted with ethyl acetate (3×15 mL) The aqueous layer was then acidified to pH 2-3 using a 1.5 N aqueous solution of HCl and extracted with EtOAc (3×15 mL). The combined organic layer was washed with water, dried over Na2SO4 and concentrated to afford Intermediate 223B as a brown oil (0.08 g, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.41 (s, 1H), 6.97-6.40 (m, 1H), 4.15-3.90 (m, 2H), 2.38-2.09 (m, 2H), 2.01-1.51 (m, 4H).

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe residue dissolved in water
3. extractionextracted with ethyl acetate (3×15 mL) The aqueous layer
4. extractionextracted with EtOAc (3×15 mL)
5. washThe combined organic layer was washed with water
6. dry with materialdried over Na2SO4
7. concentrationconcentrated

ORD record

ord-a2ae08625a4948018e24eb7b47615d95

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2