Thionyl Chloride → N-(3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide

HRID 1260806Notes

Reaction equation

HRID 1260806 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([OH:7])=O.S(Cl)(Cl)=O.[N:16]1([C:21]2[CH:22]=[C:23]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=2)[NH2:24])[CH:20]=[CH:19][N:18]=[CH:17]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[N:16]1([C:21]2[CH:22]=[C:23]([NH:24][C:5](=[O:7])[C:4]3[CH:8]=[CH:9][C:10]([CH3:11])=[C:2]([I:1])[CH:3]=3)[CH:25]=[C:26]([C:28]([F:30])([F:31])[F:29])[CH:27]=2)[CH:20]=[CH:19][N:18]=[CH:17]1

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 6216403-Iodo-4-methylbenzoic acidHCID 442226373-(1H-Imidazol-1-YL)-5-(trifluoromethyl)aniline

Product 1

HCID 44222638N-(3-(1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamideYield 84.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-Iodo-4-methylbenzoic acid (3.07 g, 0.0117 mol) was added thionyl chloride (10 mL) and refluxed for 2 h. The excess thionyl chloride was carefully removed and the resulting acid chloride was dried in vacuo for 2 h. The residue was then dissolved in DCM (anhydrous, 25 mL) and cooled on ice. To the cooled solution was added 3-(1H-imidazol-1-yl)-5-(trifluoromethyl)aniline 5 (3.46 g, 0.0152 mol) in DCM followed by the dropwise addition of diisopropylethylamine (8.2 mL, 0.047 mol). This was stirred at ambient temperature for 21 h. The white solid that separated was filtered and washed with water and dried to provide 4.65 g of product. Additional product could be obtained from the filtrate following concentration and purification by silica gel flash chromatography in EtOAc/hexanes.

Workup

  1. temperaturerefluxed for 2 h
  2. customThe excess thionyl chloride was carefully removed
  3. dry with materialthe resulting acid chloride was dried in vacuo for 2 h
  4. dissolutionThe residue was then dissolved in DCM (anhydrous, 25 mL)
  5. temperaturecooled on ice
  6. customThe white solid that separated
  7. filtrationwas filtered
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-6f5b917a59174b5b87de9c38470a49b8
Source dataset
uspto-grants-2013_06
Patent number
US08470851B2

Reaction notes

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