2,2,2-Trifluoroethanol → (R)-N-((S)-1-(2,5-difluoro-4-(2,2,2-trifluoroethoxy)phenyl)ethyl)-2-methylpropane-2-sulfinamide

Temperatur

78 °C

To a mixture of ethyl 2-oxocyclohexanecarboxylate (58.0 mg, 0.341 mmol), (R)—N—((S)-1-(4-bromo-2,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (580 mg, 1.705 mmol), Cs2CO3 (1555 mg, 4.77 mmol), copper(I) iodide (32.5 mg, 0.170 mmol) was added 2,2,2-trifluoroethanol (871 μl, 11.93 mmol). The reaction was sealed and heated at 78° C. for 24 hours. LCMS indicated complete conversion to product. The reaction mixture was then cooled to room temperature and diluted with EtOAc (20 mL). The mixture was filtered through a pad of celite and the pad was rinsed with EtOAc (20 mL). The organic was washed with water (2×15 mL), dried (Na2SO4) and concentrated. The residue was then filtered through a pad of silica gel (30 g) with EtOAc/heptane (1:3) to give crude (R)—N—((S)-1-(2,5-difluoro-4-(2,2,2-trifluoroethoxyl)phenyl)ethyl)-2-methylpropane-2-sulfinamide (0.601 g). LCMS (B) m/z 360.1 (M+H)+

1. customThe reaction was sealed
2. temperatureThe reaction mixture was then cooled to room temperature
3. filtrationThe mixture was filtered through a pad of celite
4. washthe pad was rinsed with EtOAc (20 mL)
5. washThe organic was washed with water (2×15 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated
8. filtrationThe residue was then filtered through a pad of silica gel (30 g) with EtOAc/heptane (1:3)

ORD-Eintrag

ord-126b2f9c067345d499ca80a3604009f7

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434719B2