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

HRID 1666433ノート

反応式

HRID 1666433 の反応式
[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

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 27611975-Bromo-2-(trifluoromethyl)pyridine2 回HCID 53485958Tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate

生成物 1

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

試薬・触媒・溶媒 2

HCID 11068737tetrakis(acetonitrile)copper(I) hexafluorophosphate触媒HCID 1140Toluene溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-3a14bf4a10c54e588ea966e849cdbf51
出典データセット
uspto-grants-2011_10
特許番号
US08044052B2

反応ノート

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