Trifluoroacetic acid → (4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanone

HRID 2359120Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2359120
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([N:18]1[C:22]2[CH:23]=[C:24]([C:27]3[CH2:28][CH2:29][N:30]([C:33]([C@H:35]4[CH2:40][CH2:39][CH2:38][CH2:37][N:36]4C(OC(C)(C)C)=O)=[O:34])[CH2:31][CH:32]=3)[CH:25]=[CH:26][C:21]=2[N:20]=[CH:19]1)[CH3:17]>ClCCl>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[C@H:16]([N:18]1[C:22]2[CH:23]=[C:24]([C:27]3[CH2:28][CH2:29][N:30]([C:33]([C@H:35]4[CH2:40][CH2:39][CH2:38][CH2:37][NH:36]4)=[O:34])[CH2:31][CH:32]=3)[CH:25]=[CH:26][C:21]=2[N:20]=[CH:19]1)[CH3:17]

Komponenten

4

Edukt 2

HCID 6422Trifluoroacetic acidHCID 86688431(R)-t-butyl 2-(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidine-1-carboxylate

Produkt 1

HCID 71569868(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-5,6-dihydropyridin-1(2H)-yl)((R)-piperidin-2-yl)methanoneAusbeute 88,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Trifluoroacetic acid (2 mL) was added to a solution of (R)-t-butyl 2-(4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-1,2,3,6-tetrahydropyridine-1-carbonyl)piperidine-1-carboxylate (1.5 g, 2.6 mmol) in dichloromethane (8 mL) at 0° C. under nitrogen. The reaction mixture was stirred at room temperature for 1 h. Excess solvent was removed in vacuo, and the residue was diluted with dichloromethane (30 mL). The organic layer was neutralized with saturated aqueous sodium bicarbonate, and the aqueous layer was further extracted with dichloromethane (2×30 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 3-10% methanol in dichloromethane) to give the title compound as a white solid (1.1 g, 2.3 mmol, 83%). 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1 H), 7.74 (d, J=8.4 Hz, 1 H), 7.47 (d, J=1.9 Hz, 1 H), 7.25-7.21 (m, 1 H), 7.16-7.13 (m, 1 H), 7.04 (s, 1 H), 6.86 (d, J=8.4 Hz, 1 H), 6.00-5.93 (m, 2 H), 4.29-4.07 (m, 2 H), 3.86-3.66 (m, 2 H), 3.30-3.26 (m, 1 H), 2.82-2.50 (m, 3 H), 1.99 (d, J=7.0 Hz, 3 H), 1.97-1.52 (m, 8 H); MS: (ES) m/z calculated for C26H29Cl2N4O [M+H]+ 483.2. found 483.

Aufarbeitung

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane (30 mL)
  3. extractionthe aqueous layer was further extracted with dichloromethane (2×30 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (SiO2, 3-10% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-c95194e273ea4eecbb2a55b83a2ae048
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08685959B2

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