Dichloromethane → Trifluoroacetic acid

HRID 1096650Notes

Reaction equation

HRID 1096650 reaction equation
[CH2:1]([O:3][C:4]1[S:5][CH:6]=[C:7]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]([NH:40]C(=O)OC(C)(C)C)[CH2:17][C:18]([N:20]3[CH2:25][CH2:24][CH2:23][C@@H:22]([C:26]4[N:30]([CH2:31][CH2:32][CH2:33][O:34][CH3:35])[C:29]5[CH:36]=[CH:37][CH:38]=[CH:39][C:28]=5[N:27]=4)[CH2:21]3)=[O:19])=[CH:11][CH:10]=2)[N:8]=1)[CH3:2].ClCCl.[F:51][C:52]([F:57])([F:56])[C:53]([OH:55])=[O:54]>CO.CC#N.O>[NH2:40][C@H:16]([CH2:15][C:12]1[CH:11]=[CH:10][C:9]([C:7]2[N:8]=[C:4]([O:3][CH2:1][CH3:2])[S:5][CH:6]=2)=[CH:14][CH:13]=1)[CH2:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C@@H:22]([C:26]2[N:30]([CH2:31][CH2:32][CH2:33][O:34][CH3:35])[C:29]3[CH:36]=[CH:37][CH:38]=[CH:39][C:28]=3[N:27]=2)[CH2:21]1)=[O:19].[F:51][C:52]([F:57])([F:56])[C:53]([OH:55])=[O:54]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791789HCID 66791789, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 56933295HCID 56933295, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl (R)-1-(4-(2-ethoxythiazol-4-yl)phenyl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (97B) (0.091 mmol max, 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 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 (10-55% 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 (R)-3-amino-4-(4-(2-ethoxythiazol-4-yl)phenyl)-1-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one (200) as its trifluoroacetic acid salt as a white flocculent solid (0.061 mmol, 0.041 g, 67% yield over 2-steps). ESI-MS: 562.2 m/z (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39-1.66 (m, 1H) 1.67-2.12 (m, 5H) 2.28-2.44 (m, 2H) 2.56-2.95 (m, 4H) 2.94-3.28 (m, 7H) 3.84-4.05 (m, 1H) 4.09 (d, J=1.77 Hz, 5H) 4.44-4.61 (m, 1 H) 7.09-7.60 (m, 7H) 7.70-7.93 (m, 2H).

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 (10-55% 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-9362d884dfaf43148b6265e311848226
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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