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

HRID 913151

Reaktionsgleichung

Reaktionsgleichung von HRID 913151
[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]

Komponenten

7

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 634876Binap, (A+-)-KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-ab6421cf164e4204894db637ac51dfa3
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026255B2

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