Dichloromethane → Trifluoroacetic acid

HRID 1096607Notes

Reaction equation

HRID 1096607 reaction equation
[Cl:1][C:2]1[C:7]2[N:8]([CH2:40][CH2:41][CH2:42][O:43][CH3:44])[C:9]([C@@H:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:17](=[O:39])[CH2:18][C@H:19]([NH:31]C(=O)OC(C)(C)C)[CH2:20][C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH:22]=4)[CH2:12]3)=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.ClCCl.[F:48][C:49]([F:54])([F:53])[C:50]([OH:52])=[O:51]>CO.CC#N.O>[NH2:31][C@H:19]([CH2:20][C:21]1[CH:30]=[CH:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=1)[CH2:18][C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@@H:11]([C:9]2[N:8]([CH2:40][CH2:41][CH2:42][O:43][CH3:44])[C:7]3[C:2]([Cl:1])=[CH:3][CH:4]=[CH:5][C:6]=3[N:10]=2)[CH2:12]1)=[O:39].[F:48][C:49]([F:54])([F:53])[C:50]([OH:52])=[O:51]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791714HCID 66791714, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 56933162HCID 56933162, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl (R)-4-((R)-3-(7-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (0.111 mmol max, crude oil from Step F) was added to a 10 mL round-bottomed flask equipped for stirring under nitrogen. Dichloromethane (1 mL) and trifluoroacetic acid (1 mL) were then added and the resultant solution was allowed to stir under nitrogen for 4 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 LC/MS (25-65% 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-1-((R)-3-(7-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one (97) as its trifluoroacetic acid salt as a white flocculent solid (0.052 mmol, 0.033 g, 47% over 3-steps) 1H NMR (400 MHz, DMSO-d6) δ ppm 1.35-1.56 (m, 1H) 1.63-2.14 (m, 5H) 2.60-2.78 (m, 2H) 2.88-3.42 (m, 9H) 3.69-4.01 (m, 3H) 4.00-4.61 (m, 5H) 7.10-7.30 (m, 2H) 7.42-7.60 (m, 4H) 7.73-7.99 (m, 4H) ESI-MS: m/z 519.2 (M+H)+.

Workup

  1. customequipped
  2. stirringto stir under nitrogen for 4 HR
  3. customThe solvent was removed in-vacuo
  4. customaffording a clear colored oil
  5. filtrationfiltered
  6. custompurified by preparative LC/MS (25-65% 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-598c0bc86eb847a0ba0a2a76e33bb39f
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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