Dichloromethane → Trifluoroacetic acid

HRID 1096613Notes

Reaction equation

HRID 1096613 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]3[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:38])[CH2:17][C@H:18]([NH:30]C(=O)OC(C)(C)C)[CH2:19][C:20]4[CH:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH:21]=4)[CH2:11]3)[N:7]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[C:6]=2[CH:44]=1.ClCCl.[F:48][C:49]([F:54])([F:53])[C:50]([OH:52])=[O:51]>CO.CC#N.O>[NH2:30][C@H:18]([CH2:19][C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=1)[CH2:17][C:16]([N:12]1[CH2:13][CH2:14][CH2:15][C@@H:10]([C:8]2[N:7]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[C:6]3[CH:44]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[N:9]=2)[CH2:11]1)=[O:38].[F:48][C:49]([F:54])([F:53])[C:50]([OH:52])=[O:51]

Participants

8

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 66791487tert-Butyl (R)-4-((R)-3-(6-chloro-1-(3-methoxypropyl)-1H-benz o[d]imidazol-2-yl)piperidine-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate

Product 2

HCID 6422Trifluoroacetic acidHCID 66786439(R)-3-amino-1((R)-3-(6-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

tert-Butyl (R)-4-((R)-3-(6-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-1-(naphthalen-2-yl)-4-oxobutan-2-ylcarbamate (32E) (0.135 mmol max, crude oil) 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 (15-55% 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-1-((R)-3-(6-chloro-1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)-4-(naphthalen-2-yl)butan-1-one (99) as its trifluoroacetic acid salt and as a white flocculent solid (0.074 mmol, 0.047 g, 55% yield over 3-steps). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.54 (m, 1H) 1.68-2.11 (m, 5H) 2.61-2.77 (m, 3H) 2.88-3.44 (m, 9H) 3.71-4.04 (m, 2H) 4.07-4.23 (m, 1H) 4.25-4.39 (m, 1H) 4.49 (dd, J=36.51, 13.26 Hz, 1H) 7.21-7.31 (m, 1H) 7.44 (ddd, J=8.40, 4.61, 1.64 Hz, 1H) 7.47-7.56 (m, 2H) 7.61 (dd, J=17.43, 8.59 Hz, 1H) 7.71-8.06 (m, 5H). ESI-MS: m/z 519.4 (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 (15-55% 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-e1aac6f1b4024c27b8e087cb134704a6
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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