Dichloromethane → Trifluoroacetic acid

HRID 1096644Notes

Reaction equation

HRID 1096644 reaction equation
[C:1]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C@@H:8]([NH:32]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]=[CH:31][C:20]=4[N:19]=3)[CH2:13]2)=[O:11])[CH:2]=1.C(Cl)Cl.[F:49][C:50]([F:55])([F:54])[C:51]([OH:53])=[O:52]>CO.CC#N.O>[NH2:32][C@H:8]([CH2:7][C:3]1[CH:2]=[C:1]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:6]=[CH:5][CH:4]=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]=[CH:31][C:20]=3[N:19]=2)[CH2:13]1)=[O:11].[F:49][C:50]([F:55])([F:54])[C:51]([OH:53])=[O:52]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791559HCID 66791559, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 56933200HCID 56933200, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl(R)-1-(biphenyl-3-yl)-4-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-oxobutan-2-ylcarbamate (52A) (0.05 mmol, 0.030 g) was weighed into a 20 mL round-bottomed flask equipped for stirring under nitrogen. CH2Cl2 (1 mL) and trifluoroacetic acid (1 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 (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 (R)-3-amino-4-(biphenyl-3-yl)-1-((R)-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)butan-1-one (122) as its trifluoroacetic acid salt and as a white flocculent solid (0.021 mmol, 0.013 g, 42% yield). 1H NMR (400 MHz, DMSO-d5) δ ppm 1.39-1.58 (m, 1H) 1.73-2.15 (m, 5H) 2.60-2.88 (m, 4H) 2.90-3.13 (m, 4H) 3.15-3.25 (m, 3H) 3.30-3.51 (m, 3H) 4.07-4.32 (m, 2H) 4.34-4.68 (m, 3H) 7.23-7.32 (m, 1H) 7.33-7.52 (m, 6H) 7.54-7.61 (m, 2H) 7.62-7.80 (m, 4H). ESI-MS: m/z 511.2 (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 (20-55% 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-1aea36fff6a84a8aa7b01ad1fa9cff8e
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

Loading…