Cesium carbonate → 1,1-Dimethylethyl 4-[[3-[[6-(trifluoromethyl)-3-pyridinyl]oxy]phenyl]methylene]-1-piperidinecarboxylate

HRID 1666433노트

반응식

HRID 1666433 반응식
[OH:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=1)[CH:5]=[C:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.Br[C:23]1[CH:24]=[CH:25][C:26]([C:29]([F:32])([F:31])[F:30])=[N:27][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC#N.CC#N.CC#N.CC#N.F[P-](F)(F)(F)(F)F.[Cu+]>[F:30][C:29]([F:32])([F:31])[C:26]1[N:27]=[CH:28][C:23]([O:1][C:2]2[CH:3]=[C:4]([CH:19]=[CH:20][CH:21]=2)[CH:5]=[C:6]2[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:10][CH2:11]2)=[CH:24][CH:25]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 27611975-Bromo-2-(trifluoromethyl)pyridine2회HCID 53485958Tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate

생성물 1

HCID 668757901,1-Dimethylethyl 4-[[3-[[6-(trifluoromethyl)-3-pyridinyl]oxy]phenyl]methylene]-1-piperidinecarboxylate수율 47%

시약·촉매·용매 2

HCID 11068737tetrakis(acetonitrile)copper(I) hexafluorophosphate촉매HCID 1140Toluene용매

실험 절차

A mixture of tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate (0.200 g), 5-bromo-2-(trifluoromethyl)pyridine (0.156 g, 1.00 equiv), cesium carbonate (0.450 g, 2.00 equiv), and tetrakis(acetonitrile)copper(I) hexafluorophosphate (0.019 g, 0.074 equiv) in toluene (3 mL, 0.2 M) was heated to reflux for 12 h. Additional catalyst (0.02 g) and 5-bromo-2-(trifluoromethyl)pyridine (0.200 g) was added and the mixture was refluxed for an additional 6 h. The reaction was allowed to cool to room temperature and filtered through Celite washing with ethyl acetate. Water was added and the mixture was extracted with ethyl acetate (2×). The combined organic extract was washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (10% ethyl acetate/dichloromethane) to give the title compound as a white solid (0.141 g, 47% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.47 (9H, s), 2.32 (2H, t, J=5.6 Hz), 2.44 (2H, t, J=5.6 Hz), 3.41 (2H, t, J=5.8 Hz), 3.50 (2H, t, J=5.8 Hz), 6.32 (1H, s), 6.87-6.96 (2H, m), 7.06 (1H, d, J=7.6 Hz), 7.32-7.39 (2H, m), 7.62 (1H, d, J=8.6 Hz), 8.46 (1H, d, J=2.7 Hz).

후처리

  1. temperaturewas heated
  2. temperatureto reflux for 12 h
  3. temperaturethe mixture was refluxed for an additional 6 h
  4. filtrationfiltered through Celite
  5. washwashing with ethyl acetate
  6. additionWater was added
  7. extractionthe mixture was extracted with ethyl acetate (2×)
  8. extractionThe combined organic extract
  9. washwas washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel chromatography (10% ethyl acetate/dichloromethane)

출처 및 근거

ORD 기록
ord-3a14bf4a10c54e588ea966e849cdbf51
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044052B2

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