Trifluoroacetic acid → Trifluoroacetic acid

HRID 1096600Notes

Reaction equation

HRID 1096600 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[C:7]1[C@@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([C:21](=[O:43])[CH2:22][C@H:23]([NH:35]C(=O)OC(C)(C)C)[CH2:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)[CH2:16]1.[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]>C(Cl)Cl.CO.CC#N.O>[NH2:35][C@H:23]([CH2:24][C:25]1[CH:34]=[CH:33][C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=1)[CH2:22][C:21]([N:17]1[CH2:18][CH2:19][CH2:20][C@@H:15]([C:7]2[N:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[N:8]=2)[CH2:16]1)=[O:43].[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]

Participants

8

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66791589tert-butyl (R)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

Product 2

HCID 6422Trifluoroacetic acidHCID 66784730(R)-3-amino-1((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (R)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (7E) (0.257 mmol, 0.150 g) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen and dissolved in CH2Cl2 (2 mL). Trifluoroacetic acid (2 mL) was 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 CH3CN in H2O (25-95%). 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-1((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one (74) as its trifluoroacetic acid salt and as a white flocculent solid (0.152 mmol, 0.091 g, yield 59%) 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42-1.56 (m, 1H) 1.75-2.00 (m, 3H) 2.03-2.18 (m, 2H) 2.62-2.75 (m, 3H) 2.90-3.00 (m, 1H) 3.03-3.29 (m, 8H) 3.34-3.45 (m, 2H) 3.77-3.87 (m, 2H) 4.09-4.68 (m, 3H) 7.42-7.55 (m, 5H) 7.72-8.02 (m, 6H) ESI-MS: 485.5 m/z (M+H)+.

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 CH3CN in H2O (25-95%)
  7. customThe resultant fractions were collected
  8. customthe solvent was removed in-vacuo
  9. customaffording a clear colored oil

Sources & evidence

ORD record
ord-7fce6af377894e0eb8bb3a94f009bb21
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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