4-Chloroaniline → Ethyl 4-[4-chloro-2-[(4-chlorophenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

HRID 1628407Notes

Reaction equation

HRID 1628407 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:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1>CN1CCCC1=O.C(OCC)(=O)C>[Cl:19][C:18]1[C:4]2[N:3]=[C:2]([NH:30][C:29]3[CH:31]=[CH:32][C:26]([Cl:25])=[CH:27][CH:28]=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

5

Reactant 2

HCID 78124-ChloroanilineHCID 68761768Ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate

Product 1

HCID 68762625Ethyl 4-[4-chloro-2-[(4-chlorophenyl)amino]-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoateYield 48.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of ethyl 4-[2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]butanoate (Reference Example 33; 1.00 g, 2.70 mmol) and 4-chloroaniline (1.04 g, 8.09 mmol) in 1-methyl-2-pyrrolidinone (10 mL) was stirred at 150° C. for 12 hr. After cooling, the mixture was diluted with ethyl acetate and washed with 1N hydrochloric acid, water and brine. Organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 10-25% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound (600 mg, 1.30 mmol, 48%) as a colorless solid.

Workup

  1. temperatureAfter cooling
  2. washwashed with 1N hydrochloric acid, water and brine
  3. dry with materialOrganic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel eluting with a 10-25% ethyl acetate/n-hexane gradient mixture
  6. concentrationThe filtrate was concentrated in vacuo
  7. customto give the solid, which
  8. customwas recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-75a4758cc8534e9792071ccb6ba223c8
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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