Sodium Hydroxide → 3-(difluoromethyl)cyclobutane-1-carboxylic acid

To a stirred solution of Intermediate 252A (0.2 g, 1.122 mmol) in THF (5 mL) was added NaOH (0.112 g, 2.81 mmol) in water (2 mL) at RT. After 16 h, THF was removed under a reduced pressure and the pH of aqueous solution was adjusted to 3 using a 1.0 N aq. solution of HCl and extracted with ethyl acetate (3×10 mL). The combined organic layer was washed with water, brine, dried over Na2SO4, filtered and the filtrate concentrated to afford Intermediate 252B as yellow liquid (0.12 g, 71%, mixture of cis and trans isomers). The crude product was used in a subsequent reaction without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.01-12.22 (m, 1H), 5.84-6.32 (m, 1H), 2.97-3.13 (m, 1H), 2.59-2.77 (m, 1H), 2.06-2.32 (m, 4H).

1. customTHF was removed under a reduced pressure
2. extractionextracted with ethyl acetate (3×10 mL)
3. washThe combined organic layer was washed with water, brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated

ORDレコード

ord-9056ff840e9e43c4b1b8c47799148d83

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09273058B2