Triethylamine → 5-(4-chloro-phenyl)-4-cyclopentylmethyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazole

HRID 719128Notes

Reaction equation

HRID 719128 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH2:17])[CH:9]([NH2:16])[CH2:10][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:4][CH:3]=1.Cl.[CH2:19]([O:21][C:22]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:23]=1[C:24](=N)OCC)[CH3:20].C(N(CC)CC)C>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[NH:17][C:24]([C:23]3[CH:29]=[CH:30][C:31]([O:33][CH3:34])=[CH:32][C:22]=3[O:21][CH2:19][CH3:20])=[N:16][CH:9]2[CH2:10][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 21896882HCID 21896882, compoundHCID 21896896HCID 21896896, compound

Product 1

HCID 1784670165-(4-chloro-phenyl)-4-cyclopentylmethyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazoleYield 63%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(4-chloro-phenyl)-3-cyclopentyl-propane-1,2-diamine (170 mg, 0.672 mmol) and ethyl 2-ethoxy-4-methoxy-benzimidate hydrochloride (210 mg, 0.806 mmol) in ethanol (10 mL) was added triethylamine (82 μL, 0.806 mmol). The reaction mixture was heated at gentle reflux for 6 h. The solvent was removed and the residue was partitioned between water and methylene chloride. The product was extracted with methylene chloride (2×20 mL). The organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Biotage system, KP-Sil™ 32–63 μm, 60 Å silica gel) eluting with ethyl acetate then 5–10% methanol in ethyl acetate to give 5-(4-chloro-phenyl)-4-cyclopentylmethyl-2-(2-ethoxy-4-methoxy-phenyl)-4,5-dihydro-1H-imidazole (174 mg, 63%, 4.5:1.0 ratio of cis:trans) as a white foam. HR-MS (ES, m/z) observed 413.1993, calculated for C24H30N2O2Cl [(M+H)+] 413.1991.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat gentle reflux for 6 h
  3. customThe solvent was removed
  4. customthe residue was partitioned between water and methylene chloride
  5. extractionThe product was extracted with methylene chloride (2×20 mL)
  6. washThe organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (Biotage system, KP-Sil™ 32–63 μm, 60 Å silica gel)
  10. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-883c337fc3974f7c8f7750aa2ff2247b
Source dataset
uspto-grants-2006_11
Patent number
US07132421B2

Reaction notes

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