Triphenylphosphine → 4-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester

HRID 1020041

Reaktionsgleichung

Reaktionsgleichung von HRID 1020041
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:27]([O:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17](=[O:26])[NH:18][C:19]2[CH:24]=[C:23]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[O:34][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:22]=[CH:21][N:20]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 3

HCID 11776TriphenylphosphineHCID 2773253(2-(Benzyloxy)phenyl)boronic acidHCID 595089554-(6-Chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester

Produkt 1

HCID 595091004-[6-(2-Benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl esterAusbeute 62,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 10340Sodium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a stirred mixture of 4-(6-chloro-pyrimidin-4-ylcarbamoyl)-piperidine-1-carboxylic acid benzyl ester (VIII) (0.74 g, 2.0 mmol) and 2-benzyloxyphenylboronic acid (0.50 g, 2.2 mmol) in saturated sodium carbonate solution (4 ml) and 1,4-dioxane (4 ml) was added palladium(II) acetate (0.09 g, 0.40 mmol) followed by triphenylphosphine (0.105 g, 0.400 mmol) at room temperature under an atmosphere of nitrogen. The resulting mixture was heated to reflux at 110° C. for one hour and monitored by TLC. The reaction mixture was filtered through a celite bed and the filtrate was extracted with ethyl acetate (3×100 ml). The organic layers were separated, combined, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative HPLC to afford 4-[6-(2-benzyloxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester (XVI) (0.65 g, 62%).

Aufarbeitung

  1. temperatureThe resulting mixture was heated
  2. filtrationThe reaction mixture was filtered through a celite bed
  3. extractionthe filtrate was extracted with ethyl acetate (3×100 ml)
  4. customThe organic layers were separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-9048178595954ca5af9fb2080a2ed72c
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716296B2

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