Trifluoroacetic acid → HCID 86688459, compound

HRID 1747186Notes

Reaction equation

HRID 1747186 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]=[N: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]=[N:19]1)[CH3:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86688460HCID 86688460, compound

Product 1

HCID 86688459HCID 86688459, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (0.5 mL) was added to a solution of crude (R)-t-butyl 2-((S)-4-(1-((R)-1-(2,4-dichlorophenyl)ethyl)-1H-benzo[d][1,2,3]triazol-6-yl)-2-(hydroxymethyl)piperazine-1-carbonyl)pyrrolidine-1-carboxylate (0.065 g, 0.11 mol) in dichloromethane (1.5 mL) and the resulting mixture 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 (2×20 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, 5-20% methanol in dichloromethane) to give the title compound as a white solid (0.032, 0.064 mol, 59%). 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J=9.2 Hz, 1 H), 7.41 (s, 1 H), 7.16-7.15 (m, 2 H), 7.03 (dd, J=2.0, 8.8 Hz, 1 H), 6.57 (s, 1 H), 6.24 (q, J=6.8 Hz, 1H), 4.78-4.74 (m, 1 H), 4.02-3.76 (m, 4 H), 3.62-3.54 (m, 2 H), 3.22-3.16 (m, 1 H), 2.98-2.87 (m, 3 H), 2.14 (d, J=6.8 Hz, 3 H), 1.96-1.73 (m, 6 H); MS: (ES) m/z calculated for C24H29Cl2N6O2 [M+H]+503.2, found 503.4.

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 (2×20 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, 5-20% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bf9d94d6282445ffbd3562d589eb294f
Source dataset
uspto-grants-2015_10
Patent number
US09150550B2

Reaction notes

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