(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

HRID 1629790Notes

Reaction equation

HRID 1629790 reaction equation
[F:1][C:2]([F:33])([C:25](=[O:32])[N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C:3](=[N:18][S:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[CH:6][CH:5]=1.[Si]([C:38]([F:41])([F:40])[F:39])(C)(C)C>CCCC[N+](CCCC)(CCCC)CCCC.C1C=CC([Si-](F)(F)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C.C1COCC1>[CH3:22][C:21]([S:19]([NH:18][C:3]([C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH2:12][CH2:13][C:14]([F:17])([F:16])[F:15])=[CH:8][CH:9]=1)([C:2]([F:1])([F:33])[C:25](=[O:32])[N:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1)[C:38]([F:41])([F:40])[F:39])=[O:20])([CH3:24])[CH3:23]

Participants

6

Reactant 2

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 86685882N-(2,2-Difluoro-3-oxo-3-(piperidin-1-yl)-1-(4-(4,4,4-trifluorobutoxy)phenyl)propylidene)-2-methylpropane-2-sulfinamide

Product 1

HCID 866858832-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-sulfinamideYield 58%

Reagents, catalysts & solvents 3

HCID 9893474Tetrabutylammonium DifluorotriphenylsilicateCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-4ab8790289704f8bb0c8ab0bf5545c7a
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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