Trifluoroacetic acid → HCID 71582154, compound

HRID 1747172Notes

Reaction equation

HRID 1747172 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]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][N:36]4C(OC(C)(C)C)=O)=[O:34])[C@H:29]([CH2:47][OH:48])[CH2:28]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]([N:27]3[CH2:32][CH2:31][N:30]([C:33]([C@H:35]4[CH2:39][CH2:38][CH2:37][NH:36]4)=[O:34])[C@H:29]([CH2:47][OH:48])[CH2:28]3)[CH:25]=[CH:26][C:21]=2[N:20]=[CH:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688441HCID 86688441, compound

Product 1

HCID 71582154HCID 71582154, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of (R)-t-butyl 2-((S)-4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d]imidazol-6-yl)-2-(hydroxymethyl)piperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.075 g, 0.12 mmol) in dichloromethane (2 mL) and the resulting solution was stirred at room temperature for 1 h. Excess solvent was removed in vacuo, and the residue was diluted with dichloromethane (10 mL). The organic layer was neutralized with saturated aqueous sodium bicarbonate, and the aqueous layer was further extracted with dichloromethane (2×10 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 0-20% methanol in dichloromethane) to give the title compound as a white solid (0.024 g, 0.048 mmol, 40%). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1 H), 7.67 (d, J=8.8 Hz, 1 H), 7.45 (d, J=2.0 Hz, 1 H), 7.14 (dd, J=2.4, 8.4 Hz, 1 H), 6.94 (dd, J=2.4, 8.8 Hz, 1 H), 6.85 (d, J=8.4 Hz, 1 H), 6.55 (d, J=2.0 Hz, 1 H), 5.89 (q, J=6.8 Hz, 1H), 4.76-4.72 (m, 1 H), 3.97-3.87 (m, 3 H), 3.80-3.77 (m, 1 H), 3.65-3.60 (m, 2 H), 3.44-3.41 (m, 1 H), 3.21-3.15 (m, 2 H), 2.89-2.82 (m, 2 H), 2.77-1.65 (m, 2 H), 1.96 (d, J=7.5 Hz, 3 H), 1.89-1.71 (m, 3 H); MS: (ES) m/z calculated for C25H30Cl2N5O2 [M+H]+ 502.2, found 502.4.

Workup

  1. customExcess solvent was removed in vacuo
  2. additionthe residue was diluted with dichloromethane (10 mL)
  3. extractionthe aqueous layer was further extracted with dichloromethane (2×10 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, 0-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-68b6799930954033b82edbf9464030b6
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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