Tert-Butanesulfinamide → N-(2,2-Difluoro-3-oxo-3-(piperidin-1-yl)-1-(4-(4,4,4-trifluorobutoxy)phenyl)propylidene)-2-methylpropane-2-sulfinamide

HRID 1629789Notes

Reaction equation

HRID 1629789 reaction equation
[F:1][C:2]([F:27])([C:11]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[CH:15][CH:14]=1)=O)[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].[CH3:28][C:29]([S:32]([NH2:34])=[O:33])([CH3:31])[CH3:30]>C1COCC1.[Cl-].[Na+].O.CCOC(C)=O>[F:1][C:2]([F:27])([C:3](=[O:4])[N:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)[C:11](=[N:34][S:32]([C:29]([CH3:31])([CH3:30])[CH3:28])=[O:33])[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[CH:15][CH:14]=1

Participants

6

Reactant 2

HCID 3382465Tert-ButanesulfinamideHCID 866858802,2-Difluoro-1-(piperidin-1-yl)-3-(4-(4,4,4-trifluorobutoxy)phenyl)propane-1,3-dione

Product 1

HCID 86685882N-(2,2-Difluoro-3-oxo-3-(piperidin-1-yl)-1-(4-(4,4,4-trifluorobutoxy)phenyl)propylidene)-2-methylpropane-2-sulfinamideYield 65.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of Intermediate 103B (1.97 g, 5.01 mmol) and 2-methylpropane-2-sulfinamide (1.821 g, 15.02 mmol) in anhydrous THF (25.04 mL) was added Ti(OEt)4 (5.19 mL, 25.04 mmol). The reaction was heated at refluxed temperature overnight. The reaction was cooled to rt, poured into brine, diluted with EtOAc, and stirred for 30 min. The titanium oxide was removed by filtering through a plug of Celite®. The filtrate layers were separated and the organic layer was 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 yield the desired product (1.62 g, 59%) as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.56 (d, J=8.80 Hz, 2H), 6.95 (d, J=9.08 Hz, 2H), 4.07 (t, J=6.05 Hz, 2H), 3.62-3.69 (m, 1H), 3.52-3.58 (m, 1H), 3.39 (t, J=5.09 Hz, 2H), 2.26-2.37 (m, 2H), 2.05-2.11 (m, 2H), 1.53-1.70 (m, 7H), 1.25 (s, 9H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureat refluxed temperature overnight
  3. customThe titanium oxide was removed
  4. filtrationby filtering through a plug of Celite®
  5. customThe filtrate layers were separated
  6. washthe organic layer was 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
  11. washeluted with EtOAc in hexanes

Sources & evidence

ORD record
ord-56e360d4769c46e08dae648f8fafe823
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

Loading…