Potassium Carbonate → [3-Butyl-5-(4-methoxy-phenyl)-2-phenyl-3H-imidazol-4-ylmethyl]-cyclohexylmethyl-amine

HRID 1643220Notes

Reaction equation

HRID 1643220 reaction equation
[CH2:1]([N:5]1[C:9]([CH2:10]O)=[C:8]([C:12]2[CH:17]=[CH:16][C:15](OC)=[CH:14][CH:13]=2)[N:7]=[C:6]1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:2][CH2:3][CH3:4].S(Cl)(Cl)=O.[CH:30]1([CH2:36][NH2:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.[C:38](=[O:41])([O-])[O-].[K+].[K+]>ClCCl.C(#N)C.C(OCC)(=O)C>[CH2:1]([N:5]1[C:9]([CH2:10][NH:37][CH2:36][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([O:41][CH3:38])=[CH:14][CH:13]=2)[N:7]=[C:6]1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 76688CyclohexanemethylamineHCID 588180923-Butyl-5-(4-methoxy-phenyl)-2-phenyl-3H-imidazol-4-ylmethanol

Product 1

HCID 58818024[3-Butyl-5-(4-methoxy-phenyl)-2-phenyl-3H-imidazol-4-ylmethyl]-cyclohexylmethyl-amine

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

4-({[3-Butyl-5-(4-methoxy-phenyl)-2-phenyl-3H-imidazol-4-ylmethanol (6.72 g, 20 mmol) is dissolved in 30 ml dichloromethane and cooled to 0° C., to the solution is added 5 equivalent of thionyl chloride. The resulting solution is stirred at room temperature for 2 h, the solvent and excess of thionyl chloride is evaporated. 20 ml of toluene is added to the residue and evaporated again to remove the remained thionyl chloride. The residual crude product is dissolved in 30 ml of anhydrous acetonitrile and added to an ice-cooled solution of cyclohexanemethyl amine (2.0 eq.) in 20 ml of acetonitrile containing, 2 equivalent of potassium carbonate. The resulting mixture is stirred at room temperature for 4 h, then diluted with 200 ml of ethyl acetate, washed with water and brine, dried and concentrated, the residue is purified through silica gel chromatography (hexanes/ethyl acetate, from 2:1 to 1:1) to give 11.26 g of 4-({[3-Butyl-5-(4-methoxy-phenyl)-2-phenyl-3H-imidazol-4-ylmethyl]-cyclohexylmethyl-amine. 1H NMR (400 MHz, CDCl3) δ 7.64˜7.60 (4H, m), 7.47˜7.40 (3H, m), 6.94 (2H, d, J=8.8 Hz), 4.11 (2H, m), 3.87 (2H, s), 3.84 (3H,s), 2.52 (H, d, J=6.4 Hz), 0.91˜1.77 (15H, m), 0.84 (3H, t, J=7.2 Hz); MS (+VE) m/z 432 (M+1).

Workup

  1. customthe solvent and excess of thionyl chloride is evaporated
  2. addition20 ml of toluene is added to the residue
  3. customevaporated again
  4. customto remove the remained thionyl chloride
  5. dissolutionThe residual crude product is dissolved in 30 ml of anhydrous acetonitrile
  6. additionadded to an ice-
  7. stirringThe resulting mixture is stirred at room temperature for 4 h
  8. washwashed with water and brine
  9. customdried
  10. concentrationconcentrated
  11. customthe residue is purified through silica gel chromatography (hexanes/ethyl acetate, from 2:1 to 1:1)

Sources & evidence

ORD record
ord-0c2d20128dd24cefb7cf6b011f951719
Source dataset
uspto-grants-2012_02
Patent number
US08119665B2

Reaction notes

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