Phosphorus oxychloride → Isopropyl [2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]acetate

HRID 1398739Notes

Reaction equation

HRID 1398739 reaction equation
[Cl:1][C:2]1[C:10]2[NH:9][C:8](=O)[N:7]([CH2:12][C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[C:6]=2[C:5]([CH:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:26])=O>>[Cl:26][C:8]1[N:7]([CH2:12][C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[C:6]2[C:5]([CH:19]([CH2:22][CH3:23])[CH2:20][CH3:21])=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=2[N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 86632856Isopropyl [4-chloro-7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate

Product 1

HCID 86632857Isopropyl [2,4-dichloro-7-(1-ethylpropyl)-1H-benzimidazol-1-yl]acetateYield 92%

Conditions

Temperature
100 °C

Procedure

A mixture of isopropyl [4-chloro-7-(1-ethylpropyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]acetate (14.5 g, 42.8 mmol) and phosphorus oxychloride (60 mL) was stirred at 100° C. for 3 days. After cooling, phosphorus oxychloride was evaporated in vacuo. The residue was poured into ice-cold saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate (×2). The combined organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with a 5-15% ethyl acetate/n-hexane gradient mixture to give the title compound (14.1 g, 39.5 mmol, 92%) as an oil.

Workup

  1. temperatureAfter cooling
  2. customphosphorus oxychloride was evaporated in vacuo
  3. additionThe residue was poured into ice-cold saturated aqueous sodium hydrogen carbonate
  4. extractionextracted with ethyl acetate (×2)
  5. washThe combined organic layer was washed with water and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with a 5-15% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-b2ddccd2305448399bee35df9bfcebcc
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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