Trifluoroacetic acid → Trifluoroacetic acid

HRID 1096646Notes

Reaction equation

HRID 1096646 reaction equation
C(OC([NH:8][C@@H:9]([CH2:27][C:28]([N:30]1[CH2:35][CH2:34][CH2:33][C@@H:32]([C:36]2[N:40]([CH2:41][CH2:42][CH2:43][O:44][CH3:45])[C:39]3[CH:46]=[CH:47][CH:48]=[CH:49][C:38]=3[N:37]=2)[CH2:31]1)=[O:29])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:25][CH3:26])=[O:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)=O)(C)(C)C.[F:50][C:51]([F:56])([F:55])[C:52]([OH:54])=[O:53]>C(Cl)Cl.CO.CC#N.O>[NH2:8][C@@H:9]([CH2:27][C:28]([N:30]1[CH2:35][CH2:34][CH2:33][C@@H:32]([C:36]2[N:40]([CH2:41][CH2:42][CH2:43][O:44][CH3:45])[C:39]3[CH:46]=[CH:47][CH:48]=[CH:49][C:38]=3[N:37]=2)[CH2:31]1)=[O:29])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:25][CH3:26])=[O:24])=[CH:19][CH:18]=2)=[CH:13][CH:12]=1.[F:50][C:51]([F:56])([F:55])[C:52]([OH:54])=[O:53]

Participants

8

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66784669methyl 4'-((R)-2-(tert-butoxycarbonylamino)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)biphenyl-4-carboxylate

Product 2

HCID 6422Trifluoroacetic acidHCID 56933201methyl 4'-((R)-2-amino-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)biphenyl-4-carboxylate

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 4′-((R)-2-(tert-butoxycarbonylamino)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)biphenyl-4-carboxylate (53A) (0.08 mmol, 0.054 g) was weighed into a 20 mL scintillation vial and dissolved in CH2Cl2 (2 mL). Trifluoroacetic acid (2 mL) was 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 (20-55% 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 methyl 4′-((R)-2-amino-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutyl)biphenyl-4-carboxylate (123) as its trifluoroacetic acid salt and as a white flocculent solid. (0.07 mmol, 0.040 g, 88% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.40-1.63 (m, 1H) 1.73-2.21 (m, 5H) 2.56-2.87 (m, 3H) 2.91-3.15 (m, 3H) 3.16-3.52 (m, 5H) 3.68-3.92 (m, 4H) 4.05-4.70 (m, 5H) 7.37-7.53 (m, 4H) 7.68-7.87 (m, 6H) 8.02-8.07 (m, 2H). ESI-MS: 569.3 m/z (M+H)+.

Workup

  1. customThe solvent was removed in-vacuo
  2. customaffording a clear colored oil
  3. filtrationfiltered
  4. custompurified by preparative LC/MS (20-55% CH3CN in H2O)
  5. customThe resultant fractions were collected
  6. customthe solvent was removed in-vacuo
  7. customaffording a clear colored oil

Sources & evidence

ORD record
ord-68a4566549eb4689b42b975e2976f73b
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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