Potassium Hydroxide → tert-butyl 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(3,3,3-trifluoropropyl)-1H-imidazol-2-yl)piperidine-1-carboxylate

HRID 2088933Notes

Reaction equation

HRID 2088933 reaction equation
[F:1][C:2]([F:24])([F:23])[CH2:3][CH2:4][C:5]1[N:6]=[C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[NH:8][CH:9]=1.[OH-].[K+].Cl.Cl[CH2:29][CH2:30][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1>CS(C)=O.C(OCC)(=O)C>[N:31]1([CH2:30][CH2:29][N:8]2[CH:9]=[C:5]([CH2:4][CH2:3][C:2]([F:23])([F:1])[F:24])[N:6]=[C:7]2[CH:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:14][CH2:15]2)[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 178451800HCID 178451800, compound

Product 1

HCID 67112062tert-butyl 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(3,3,3-trifluoropropyl)-1H-imidazol-2-yl)piperidine-1-carboxylateYield 25.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Combine tert-butyl 4-(4-(3,3,3-trifluoropropyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (2.27 g, 6.53 mmol), potassium hydroxide (1.20 g, 3.3 eq) (freshly powdered), and 1-(2-chloroethyl)pyrrolidine hydrochloride (1.34 g, 1.2 eq) in dimethyl sulfoxide (100 mL). Heat the reaction mixture at 50° C. overnight, then allow to cool to room temperature. Dilute with ethyl acetate. Wash with water followed by saturated aqueous sodium chloride. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by silica gel chromatography, eluting with 4:1 dichloromethane:isopropyl alcohol, to give tert-butyl 4-(1-(2-(pyrrolidin-1-yl)ethyl)-4-(3,3,3-trifluoropropyl)-1H-imidazol-2-yl)piperidine-1-carboxylate as a thick yellow oil (0.73 g, 25%). MS (ES) m/z=445 [M]+.

Workup

  1. temperatureto cool to room temperature
  2. washWash with water
  3. dry with materialDry the organics over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify by silica gel chromatography
  7. washeluting with 4:1 dichloromethane

Sources & evidence

ORD record
ord-08b80ffa81f54ebe930c0a303c8158bc
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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