3,5-Dichloroaniline → HCID 68764099, compound

HRID 1398766Notes

Reaction equation

HRID 1398766 reaction equation
Cl[C:2]1[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=[C:18]([Cl:19])[C:4]=2[N:3]=1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:30]=[C:31]([Cl:33])[CH:32]=1)[NH2:29].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CN1CCCC1=O>[Cl:19][C:18]1[C:4]2[N:3]=[C:2]([NH:29][C:28]3[CH:27]=[C:26]([Cl:25])[CH:32]=[C:31]([Cl:33])[CH:30]=3)[N:6]([CH2:7][CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]=2[C:15]([CH:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 122813,5-DichloroanilineHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

Product 1

HCID 68764099HCID 68764099, compoundYield 40.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 500 mg, 1.35 mmol), 3,5-dichloroaniline (655 mg, 4.04 mmol) and p-toluenesulfonic acid monohydrate (257 mg, 1.35 mmol) in 1-methyl-2-pyrrolidinone (4 mL) was irradiated by microwave at 180° C. for 15 min. After cooling, aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give a residue, which was purified by preparative HPLC to give the title compound (270 mg, 0.542 mmol, 40%) as a colorless amorphous.

Workup

  1. customwas irradiated by microwave at 180° C. for 15 min
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washOrganic layer was washed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel eluting with a 5-20% ethyl acetate/n-hexane gradient mixture
  8. concentrationThe filtrate was concentrated in vacuo
  9. customto give a residue, which
  10. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-57c9668c44e24260b8306d8e74de1ace
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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