(Trifluoromethyl)trimethylsilane → 2-Methyl-N-(1,1,1,3,3-pentafluoro-4-oxo-4-(piperidin-1-yl)-2-(4-(4,4,4-trifluorobutoxy)phenyl)butan-2-yl)propane-2-sulfinamide

Temperatur

0 °C

To a solution of TBAT (3.43 g, 6.36 mmol) in DMF (5.89 mL) was added a solution of Intermediate 103C (1.17 g, 2.356 mmol) in THF (5.89 mL). The solution was cooled to 0° C., and then 2 M TMSCF3 (3.53 mL, 7.07 mmol) in THF was added dropwise. The reaction was stirred at 0° C. for 1 h, and then quenched with brine (20 mL) at 0° C. The mixture was warmed to rt and diluted with water and EtOAc. The layers were separated. The aqueous layer was washed with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel chromatography (80 g silica gel, eluted with EtOAc in hexanes) to afford the desired product (773 mg, 58%) as a yellow gum. LCMS Anal. Calc'd for C23H30F8N2O3S 566.18, found [M+H] 567.1. 1H NMR (500 MHz, CD3OD) δ 7.69 (d, J=8.53 Hz, 2H), 6.91 (d, J=9.08 Hz, 2H), 4.03 (t, J=5.91 Hz, 2H), 3.50-3.62 (m, 2H), 3.34-3.45 (m, 2H), 2.23-2.35 (m, 2H), 1.98-2.07 (m, 2H), 1.48-1.69 (m, 6H), 1.26 (s, 9H).

1. customquenched with brine (20 mL) at 0° C
2. temperatureThe mixture was warmed to rt
3. additiondiluted with water and EtOAc
4. customThe layers were separated
5. washThe aqueous layer was washed with EtOAc
6. washThe combined organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by silica gel chromatography (80 g silica gel, eluted with EtOAc in hexanes)

ORD-Eintrag

ord-4ab8790289704f8bb0c8ab0bf5545c7a

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08791091B2