Phenethyl bromide → 3-Benzyl 1-methyl 4-(4-(dibutylcarbamoyl)-1-phenethyl-1H-imidazol-2-yl)isophthalate

HRID 529009Notes

Reaction equation

HRID 529009 reaction equation
[CH2:1]([N:5]([CH2:33][CH2:34][CH2:35][CH3:36])[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[NH:11][CH:12]=1)=[O:7])[CH2:2][CH2:3][CH3:4].C([O-])([O-])=O.[K+].[K+].[CH:43]1[CH:48]=[CH:47][C:46]([CH2:49][CH2:50]Br)=[CH:45][CH:44]=1>CN(C=O)C.CC(OC)(C)C>[CH2:33]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:8]1[N:9]=[C:10]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][C:14]=2[C:23]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[O:24])[N:11]([CH2:50][CH2:49][C:46]2[CH:47]=[CH:48][CH:43]=[CH:44][CH:45]=2)[CH:12]=1)=[O:7])[CH2:34][CH2:35][CH3:36]

Participants

6

Reactant 3

HCID 7666Phenethyl bromideHCID 11430Potassium CarbonateHCID 178449065HCID 178449065, compound

Product 1

HCID 710610123-Benzyl 1-methyl 4-(4-(dibutylcarbamoyl)-1-phenethyl-1H-imidazol-2-yl)isophthalateYield 73.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

To a stirred solution of 3-benzyl 1-methyl 4-(4-(dibutylcarbamoyl)-1H-imidazol-2-yl)isophthalate (200 mg, 0.4 mmol) in dry DMF (5 mL) was added K2CO3 (168 mg, 1.22 mmol) and 2-phenethyl bromide (90 mg, 0.48 mmol) at 0° C. The mixture was allowed to warm to room temperature and stirred for 48 h. The reaction mixture was then cooled to 0° C., diluted with MTBE and quenched with water. The layers were separated and the aqueous layer was extracted with MTBE (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. The crude material was purified by flash chromatography (gradient from 10% to 50% EtOAc/hexanes) to provide the title compound (175 mg, 72%). 1H NMR (CDCl3) 8.65 (d, J=2.0 Hz, 1H), 8.06 (dd, J=8.0, 2.0 Hz, 1H), 7.53 (s, 1H), 7.36-7.34 (m, 3H), 7.25-7.17 (m, 5H), 6.90 (d, J=8.0 Hz, 1H), 6.81-6.79 (m, 2H), 5.14 (s, 2H), 3.99 (s, 3H), 3.97-3.95 (m, 2H), 3.67 (t, J=7.2 Hz, 2H), 3.50 (br s, 2H), 2.76 (t, J=7.2 Hz, 2H), 1.70-1.60 (m, 4H), 1.40-1.20 (m, 4H), 0.98-0.84 (m, 6H); MS(ESI+) m/z 596.2 (M+H)+.

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. customquenched with water
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with MTBE (3×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a crude oil
  9. customThe crude material was purified by flash chromatography (gradient from 10% to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-474704748eed4dee85f0e77e54d89cc7
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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