Dichloromethane → Trifluoroacetic acid

HRID 1096649Notes

Reaction equation

HRID 1096649 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C@@H:21]([NH:45]C(=O)OC(C)(C)C)[CH2:22][C:23]([N:25]3[CH2:30][CH2:29][CH2:28][C@@H:27]([C:31]4[N:35]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[C:34]5[CH:41]=[CH:42][CH:43]=[CH:44][C:33]=5[N:32]=4)[CH2:26]3)=[O:24])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)=[O:7].ClCCl.[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59]>CO.CC#N.O>[NH2:45][C@@H:21]([CH2:22][C:23]([N:25]1[CH2:30][CH2:29][CH2:28][C@@H:27]([C:31]2[N:35]([CH2:36][CH2:37][CH2:38][O:39][CH3:40])[C:34]3[CH:41]=[CH:42][CH:43]=[CH:44][C:33]=3[N:32]=2)[CH2:26]1)=[O:24])[CH2:20][C:17]1[CH:16]=[CH:15][C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:6]([NH:5][CH2:4][CH2:3][O:2][CH3:1])=[O:7])=[CH:9][CH:10]=2)=[CH:19][CH:18]=1.[F:56][C:57]([F:62])([F:61])[C:58]([OH:60])=[O:59]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791582HCID 66791582, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 66785545HCID 66785545, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-butyl (R)-1-(4′-(2-methoxyethylcarbamoyl)biphenyl-4-yl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (86B) (0.053 mmoles, 0.038 g) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. Dichloromethane (1 mL) and trifluoroacetic acid (1 mL) were then added and the resultant solution was allowed to stir under nitrogen for 4 hrs. The solvent was removed in-vacuo affording a clear colored oil. This oil was re-dissolved in Methanol (3 mL), filtered, and then purified by preparative LC/MS (0.5-50% CH3CN in H2O). The resultant fractions were collected and the solvent was removed in-vacuo affording a clear colored oil. This oil was re-dissolved in CH3CN (1 mL) and water (2 mL). The resultant solution was frozen and lyophilized to afford 4′-((R)-2-amino-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)-N-(2-methoxyethyl)biphenyl-4-carboxamide (177) as its trifluoroacetic acid salt and as a white flocculent solid (0.033 mmoles, 0.024 g, 62% yield). ESI-MS: m/z 612.3 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40-1.62 (m, 1H) 1.74-2.21 (m, 5H) 2.58-2.86 (m, 3H) 2.90-3.16 (m, 4H) 3.16-3.25 (m, 3H) 3.28 (s, 3H) 3.30-3.51 (m, 7H) 3.64-4.19 (m, 2H) 4.27-4.70 (m, 4H) 7.36-7.50 (m, 4H) 7.68-7.82 (m, 6H) 7.95 (dd, J=8.46, 2.40 Hz, 2H) 8.54-8.63 (m, 1H).

Workup

  1. customequipped
  2. stirringto stir under nitrogen for 4 hrs
  3. customThe solvent was removed in-vacuo
  4. customaffording a clear colored oil
  5. filtrationfiltered
  6. custompurified by preparative LC/MS (0.5-50% CH3CN in H2O)
  7. customThe resultant fractions were collected
  8. customthe solvent was removed in-vacuo
  9. customaffording a clear colored oil

Sources & evidence

ORD record
ord-da3fce96072a459ebc8baaa268a67d82
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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