Dichloromethane → Trifluoroacetic acid

HRID 1096643Notes

Reaction equation

HRID 1096643 reaction equation
[C:1]1([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:33]C(=O)OC(C)(C)C)[CH2:9][C:10]([N:12]2[CH2:17][CH2:16][CH2:15][C@@H:14]([C:18]3[N:22]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])[C:21]4[CH:28]=[CH:29][CH:30]=[C:31]([Cl:32])[C:20]=4[N:19]=3)[CH2:13]2)=[O:11])=[CH:3][CH:2]=1.ClCCl.[F:50][C:51]([F:56])([F:55])[C:52]([OH:54])=[O:53]>CO.CC#N.O>[NH2:33][C@H:8]([CH2:7][C:4]1[CH:3]=[CH:2][C:1]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)=[CH:6][CH:5]=1)[CH2:9][C:10]([N:12]1[CH2:17][CH2:16][CH2:15][C@@H:14]([C:18]2[N:22]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])[C:21]3[CH:28]=[CH:29][CH:30]=[C:31]([Cl:32])[C:20]=3[N:19]=2)[CH2:13]1)=[O:11].[F:50][C:51]([F:56])([F:55])[C:52]([OH:54])=[O:53]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791618HCID 66791618, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 56933197(R)-3-amino-4-(biphenyl-4-yl)-1-((R)-3-(4-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl (R)-1-(biphenyl-4-yl)-4-((R)-3-(4-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (48C) (0.245 mmol, crude oil) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. Dichloromethane (2 mL) and trifluoroacetic acid (2 mL) were then added and the solution was stirred at room temperature for 2 hr. 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 (15-65% 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 (R)-3-amino-4-(biphenyl-4-yl)-1((R)-3-(4-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one (118) as its trifluoroacetic acid salt and as a white flocculent solid (0.134 mmol, 0.088 g, 55% yield over 4-steps). ESI-MS: 545.2 m/z (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40-1.55 (m, 1H) 1.70-2.14 (m, 5H) 2.61-2.87 (m, 3H) 2.87-3.09 (m, 4H) 3.09-3.31 (m, 5H) 3.40-3.85 (m, 2H) 3.95-4.62 (m, 5H) 7.17-7.30 (m, 2H) 7.33-7.42 (m, 3H) 7.42-7.56 (m, 3H) 7.58-7.72 (m, 4H).

Workup

  1. customequipped
  2. stirringthe solution was stirred at room temperature for 2 hr
  3. customThe solvent was removed in-vacuo
  4. customaffording a clear colored oil
  5. filtrationfiltered
  6. custompurified by preparative LC/MS (15-65% 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-528024c11f8b4b71929e55a92eaad3df
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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