2-(3,3-difluorocyclobutyl)ethan-1-ol → (3,3-Difluorocyclobutyl)acetic acid

A solution of 2-(3,3-difluorocyclobutyl)ethanol (270 mg, 2.0 mmol, prepared as described in Bogen, S. et al., Bioorg. Med. Chem. Lett., 18:4219 (2008)) in acetone (5 mL) was treated with Jones reagent (2.7 mmol, 1 mL of 2.7 M solution) over a period of 30 minutes at room temperature. After 2 hours, additional Jones reagent (0.25 mL) was added. After 1 hour, the reaction mixture was filtered through CELITE®, and concentrated under reduced pressure. The reaction mixture was re-dissolved in ethyl acetate (10 mL), washed with water (2×20 mL), brine (20 mL), and then dried over MgSO4, The mixture was then filtered and concentrated to isolate Intermediate S-9A (275 mg, 92% yield) as a tan solid. 1H NMR (500 MHz, chloroform-d) δ 2.74-2.87 (2H, m), 2.57-2.62 (2H, m), 2.48-2.56 (1H, m, J=8.60, 4.30, 4.30, 1.94 Hz), 2.23-2.35 (2H, m).

1. waitAfter 1 hour
2. filtrationthe reaction mixture was filtered through CELITE®
3. concentrationconcentrated under reduced pressure
4. dissolutionThe reaction mixture was re-dissolved in ethyl acetate (10 mL)
5. washwashed with water (2×20 mL), brine (20 mL)
6. dry with materialdried over MgSO4
7. filtrationThe mixture was then filtered
8. concentrationconcentrated
9. customto isolate Intermediate S-9A (275 mg, 92% yield) as a tan solid

ORD record

ord-1760725091bd406ba1f32acdd50979ce

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09427442B2