Water → HCID 86716172, compound

To a solution of compound 4,4-difluoro-1-(pyrimidin-5-yl)-cyclohexanecarbonitrile (1.5 g, 6.72 mmol) and DFMS (6.0 g, 0.02 mol) in trifluoromethylbenzene (53 mL) and H2O (21 mL) at room temperature was added TFA (766 mg, 6.72 mmol) followed by slow addition of t-BuOOH (5.2 g, 70% solution in H2O) with vigorous stirring. The reaction mixture was stirred at room temperature overnight. TLC indicates about 50% starting material remained, a second addition of DFMS (6.0 g, 0.02 mol) and t-BuOOH(5.2 g, 70% solution in H2O) were added to the reaction mixture. Upon consumption of starting material, the reaction mixture was portioned between DCM (20 mL) and saturated NaHCO3 solution (20 mL), the organic layer was separated and the aqueous layer was extracted with DCM (3×20 ml). The organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (Petroleum ether:EtOAc=3:1) to give 1-(2-(difluoromethyl)pyrimidin-5-yl)-4,4-difluorocyclohexanecarbonitrile (800 mg, Yield: 44.4%). 1H NMR (CDCl3 400 MHz): δ9.03 (s, 2H), 6.71 (t, J=54.4 Hz, 1H), 2.40-2.27 (m, 6H).

1. additionwere added to the reaction mixture
2. customUpon consumption of starting material
3. customthe organic layer was separated
4. extractionthe aqueous layer was extracted with DCM (3×20 ml)
5. washThe organic layer was washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customThe crude product was purified by flash chromatography (Petroleum ether:EtOAc=3:1)

ORD record

ord-1db4f644980545d7bddd04aff6efa1e2

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102591B2