Methanol → 2-(3-chloro-4-fluoro-phenyl)-7-hydroxy-1H-benzoimidazole-4-carboxylic acid methyl ester

HRID 349499Notes

Reaction equation

HRID 349499 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[NH:13][C:12]3[C:14]([OH:21])=[CH:15][CH:16]=[C:17]([C:18]([OH:20])=[O:19])[C:11]=3[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].O=S(Cl)Cl.[CH3:26]O>>[CH3:26][O:19][C:18]([C:17]1[C:11]2[N:10]=[C:9]([C:4]3[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=3)[NH:13][C:12]=2[C:14]([OH:21])=[CH:15][CH:16]=1)=[O:20]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 691315522-(3-chloro-4-fluoro-phenyl)-7-hydroxy-1H-benzoimidazole-4-carboxylic acid

Product 1

HCID 691195392-(3-chloro-4-fluoro-phenyl)-7-hydroxy-1H-benzoimidazole-4-carboxylic acid methyl esterYield 81%

Procedure

2-(3-chloro-4-fluoro-phenyl)-7-hydroxy-1H-benzoimidazole-4-carboxylic acid (800 mg, 2.64 mmol) obtained in step 3 was dissolved in methanol, SOCl2 (1.93 ml, 26.41 mmol) was added dropwise thereto and refluxed for 15 hours. The resulting solution was cooled to room temperature, concentrated under a reduced pressure to remove methanol, and the residue was neutralized with NaHCO3. Then, the neutralized residue was extracted with ethyl acetate and concentrated under a reduced pressure to obtain a residue which was purified by silica gel chromatography to obtain the title compound (690 mg, 2.15 mmol) in a yield of 81%.

Workup

  1. temperaturerefluxed for 15 hours
  2. concentrationconcentrated under a reduced pressure
  3. customto remove methanol
  4. extractionThen, the neutralized residue was extracted with ethyl acetate
  5. concentrationconcentrated under a reduced pressure
  6. customto obtain a residue which
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-c99a47c3236744d5ace8b8f352251845
Source dataset
uspto-grants-2007_02
Patent number
US07179832B2

Reaction notes

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