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 2359120Notes

Reaction equation

HRID 2359120 reaction equation
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]

Participants

4

Reactant 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

Product 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)methanoneYield 88.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-c95194e273ea4eecbb2a55b83a2ae048
Source dataset
uspto-grants-2014_04
Patent number
US08685959B2

Reaction notes

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