4-Amino-1-Boc-piperidine → 4-(5-Benzyloxy-pyridin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 913151

反応式

HRID 913151 の反応式
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](Cl)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH2:29])[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].O(C(C)(C)C)[K]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:14][N:13]=2)[CH2:25][CH2:24]1)=[O:22])([CH3:19])([CH3:17])[CH3:18]

参加物

7

反応物 3

HCID 12682914-Amino-1-Boc-piperidineHCID 100137175-(Benzyloxy)-2-chloropyridineHCID 178418922HCID 178418922、化合物

生成物 1

HCID 674007704-(5-Benzyloxy-pyridin-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester収率 87%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 634876Binap, (A+-)-触媒HCID 1140Toluene溶媒

反応条件

温度
70 °C

実験手順

A stirred suspension of 5-benzyloxy-2-chloro-pyridine (12.4 g, 56.4 mmol, 1.0 equiv; prepared as described in WO 9728 128 A1 (Zeneca Ltd., UK)), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (11.31 g, 56.4 mmol, 1.0 equiv), palladium(II) acetate (0.51 g, 2.3 mmol, 0.04 equiv) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (1.44 g, 2.3 mmol, 0.04 equiv) in toluene (250 mL) was treated at rt with KOtert-Bu (6.71 g, 67.7 mmol, 1.2 equiv) and subsequently warmed to 70° C. After 7 h, the reaction mixture was poured into crashed ice and filtered over dicalite and extracted twice with toluene. The combined organic layers were dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 18.73 g (87%) of the title compound as a light yellow solid. MS (ISP): 384.1 [M+H]+.

後処理

  1. additionthe reaction mixture was poured
  2. filtrationfiltered over dicalite
  3. extractionextracted twice with toluene
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation under reduced pressure
  7. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

出典と根拠

ORDレコード
ord-ab6421cf164e4204894db637ac51dfa3
出典データセット
uspto-grants-2011_09
特許番号
US08026255B2

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