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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 1629789
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HRID 1629789 반응식
[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
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참가 물질

6

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

생성물 1

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

시약·촉매·용매 3

HCID 8028Tetrahydrofuran용매
HCID 8857
Ethyl Acetate
용매
HCID 57417360Sodium chloride; water용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-56e360d4769c46e08dae648f8fafe823
출처 데이터셋
uspto-grants-2014_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08791091B2

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