Dichloromethane → Trifluoroacetic acid

HRID 1096652Notes

Reaction equation

HRID 1096652 reaction equation
[CH:1]1([NH:7][C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C@@H:17]([NH:41]C(=O)OC(C)(C)C)[CH2:18][C:19]([N:21]3[CH2:26][CH2:25][CH2:24][C@@H:23]([C:27]4[N:31]([CH2:32][CH2:33][CH2:34][O:35][CH3:36])[C:30]5[CH:37]=[CH:38][CH:39]=[CH:40][C:29]=5[N:28]=4)[CH2:22]3)=[O:20])=[CH:12][CH:11]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.ClCCl.[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55]>CO.CC#N.O>[NH2:41][C@@H:17]([CH2:18][C:19]([N:21]1[CH2:26][CH2:25][CH2:24][C@@H:23]([C:27]2[N:31]([CH2:32][CH2:33][CH2:34][O:35][CH3:36])[C:30]3[CH:37]=[CH:38][CH:39]=[CH:40][C:29]=3[N:28]=2)[CH2:22]1)=[O:20])[CH2:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]([NH:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[O:9])=[CH:11][CH:12]=1.[F:52][C:53]([F:58])([F:57])[C:54]([OH:56])=[O:55]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791757tert-butyl (R)-1-(4-(cyclohexylcarbamoyl)phenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate

Product 2

HCID 6422Trifluoroacetic acidHCID 569333314-((R)-2-amino-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)-N-cyclohexylbenzamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

98A (0.039 mmol, 0.025 g) 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 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-cyclohexylbenzamide (203) as its trifluoroacetic acid salt and as a white flocculent solid. (0.009 mmol, 0.006 g, 24% yield). ESI-MS: 560.3 m/z (M+H)+.

Workup

  1. customequipped
  2. stirringthe solution was stirred at room temperature for 2 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-b3b9be3459d34e0c9b92ed913ff3f64b
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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