4-溴吡啶 → Ethyl 4-(pyridin-4-ylamino)piperidine-1-carboxylate

HRID 20074

反应方程式

HRID 20074 反应方程式
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.Br[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.CC(C)([O-])C.[Na+].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.[Pd+2].C([O-])(=O)C>[N:17]1[CH:18]=[CH:19][C:14]([NH:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:7]2)=[CH:15][CH:16]=1

参与物

7

反应物 4

HCID 142684-溴吡啶HCID 1008674-氨基-1-哌啶甲酸乙酯HCID 6348761,1'-联萘-2,2'-双二苯膦 (BINAP)HCID 23676156叔丁醇钠

产物 1

HCID 22293223Ethyl 4-(pyridin-4-ylamino)piperidine-1-carboxylate收率 41.1%

试剂、催化剂与溶剂 2

HCID 167845palladium acetate催化剂HCID 1140甲苯溶剂

实验过程

A solution of ethyl 4-aminopiperidine-1-carboxylate (2.20 g, 12.7 mmol), 4-bromopyridine (3.47 g, 17.8 mmol), sodium t-butoxide (4.54 g, 47.2 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.398 g, 0.639 mmol) and palladium acetate (0.143 g, 0.639 mmol) in toluene (40 mL) was heated at 60° C. overnight. The reaction was cooled and partitioned between ethyl acetate and water. The aqueous layer was washed 3 times with methylene chloride, and the combined organic layers dried over sodium sulfate. The crude product was purified by chromatography (silica gel, 0 to 10% {5% ammonium hydroxide in methanol}in methylene chloride gradient elution), which gave the title compound (1.3 g, 41% yield).

后处理

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe aqueous layer was washed 3 times with methylene chloride
  4. dry with materialthe combined organic layers dried over sodium sulfate
  5. customThe crude product was purified by chromatography (silica gel, 0 to 10% {5% ammonium hydroxide in methanol}in methylene chloride gradient elution), which

来源与证据

ORD记录
ord-101a650b45d542b081d56e34c403fdfc
来源数据集
uspto-grants-2010_06
专利号
US07745427B2

关联笔记

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