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

HRID 913151

반응식

HRID 913151 반응식
[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]

참가 물질

7

반응물 3

HCID 12682914-Amino-1-Boc-piperidineHCID 100137175-(Benzyloxy)-2-chloropyridineHCID 178418922HCID 178418922, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 634876Binap, (A+-)-촉매HCID 1140Toluene용매

반응 조건

온도
70 °C

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-ab6421cf164e4204894db637ac51dfa3
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026255B2

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