(Trifluoromethyl)trimethylsilane → HCID 86732271, compound

To a cooled solution of (R)-N-((S)-2-(2-chloro-3-fluorophenyl)-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (5.8 g, 18.14 mmol) in tetrahydrofuran (80 mL) at −78° C. was added trimethyl(trifluoromethyl)silane (26.8 mL, 181 mmol). After stirred for 20 min, tetrabutylammonium fluoride, 1.0M solution in THF (27.2 mL, 27.2 mmol) was added dropwise. After 3 h, the reaction was quenched with 1N HCl (30 ml), and then the cooling bath was removed. The reaction mixture was diluted with water (60 mL) and EtOAc (60 mL), and warmed to ambient temperature. The solution was extracted with EtOAc twice. The organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with MTBE (15 mL). The resulted solid was filtered and washed with DCM. The filtrate was concentrated in vacuo and purified by silica gel column (240 g, 0-100% EtOA/hexane in 25 min) to afford additional product. The solids were combined to give (R)-N-((2S,4S)-2-(2-chloro-3-fluorophenyl)-5,5,5-trifluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide (1.75 g, 25% yield). MS m/z=390 [M+H]+. Calculated for C15H20ClF4NO2S: 389.8.

1. waitAfter 3 h
2. customthe reaction was quenched with 1N HCl (30 ml)
3. customthe cooling bath was removed
4. additionThe reaction mixture was diluted with water (60 mL) and EtOAc (60 mL)
5. extractionThe solution was extracted with EtOAc twice
6. washThe organic extracts were washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was triturated with MTBE (15 mL)
11. filtrationThe resulted solid was filtered
12. washwashed with DCM
13. concentrationThe filtrate was concentrated in vacuo
14. custompurified by silica gel column (240 g, 0-100% EtOA/hexane in 25 min)
15. customto afford additional product

ORD record

ord-c0bbfc7f9eb74963b3d722d2e0f220d3

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2