Cesium carbonate → tert-Butyl {2-[1-(4-bromo-phenyl)piperidin-4-yl]ethyl}-carbamate

HRID 1019708

反応式

HRID 1019708 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.[NH:9]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1

参加物

10

反応物 4

HCID 10796Cesium carbonateHCID 115221-Bromo-4-iodobenzeneHCID 634876Binap, (A+-)-HCID 15018494-(2-Aminoethyl)piperidine, 4-BOC protected

生成物 1

HCID 86661351tert-Butyl {2-[1-(4-bromo-phenyl)piperidin-4-yl]ethyl}-carbamate収率 19.8%

試薬・触媒・溶媒 5

HCID 167845palladium(II) acetate触媒2 回HCID 634876Binap, (A+-)-触媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

6.19 g (21.90 mmol) of 1-bromo-4-iodobenzene, 5.00 g (21.90 mmol) of tert-butyl (2-piperidin-4-ylethyl)carbamate, 9.98 g (60.66 mmol) of caesium carbonate and 0.54 g (0.88 mmol) of BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) suspended in 100 mL of toluene are placed under an inert atmosphere. 0.098 g (0.44 mmol) of palladium diacetate is then added. The reaction mixture is then refluxed for 6 hours. 0.045 g (0.20 mmol) of palladium diacetate and 0.25 g (0.40 mmol) of BINAP are added and the mixture is left to stir at reflux for 12 hours. The reaction medium is allowed to cool, and ethyl acetate and water are added. The aqueous phase is separated out and extracted twice with ethyl acetate, and the combined organic phases are washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. After evaporating off the solvent, the residue obtained is purified by chromatography on silica gel, eluting with a 98/2/0.2 mixture of dichloromethane, methanol and 28% aqueous ammonia to give 1.66 g of expected product in the form of a white solid.

後処理

  1. temperatureThe reaction mixture is then refluxed for 6 hours
  2. waitthe mixture is left
  3. temperatureat reflux for 12 hours
  4. temperatureto cool
  5. customThe aqueous phase is separated out
  6. extractionextracted twice with ethyl acetate
  7. washthe combined organic phases are washed with saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. customAfter evaporating off the solvent
  10. customthe residue obtained
  11. customis purified by chromatography on silica gel
  12. washeluting with a 98/2/0.2 mixture of dichloromethane, methanol and 28% aqueous ammonia

出典と根拠

ORDレコード
ord-f643cf4c1c954478aff3d8023f575c2c
出典データセット
uspto-grants-2014_05
特許番号
US08716289B2

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