Acetic Acid → (7-chloro-6-fluoro-1H-benzimidazol-1-yl)acetic acid

HRID 603117Notes

Reaction equation

HRID 603117 reaction equation
[Cl:1][C:2]1[C:7]2[N:8]([CH2:11][CH2:12][OH:13])[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14].CC(O)=[O:17]>CC(O)C.OS(O)(=O)=O.O>[Cl:1][C:2]1[C:7]2[N:8]([CH2:11][C:12]([OH:17])=[O:13])[CH:9]=[N:10][C:6]=2[CH:5]=[CH:4][C:3]=1[F:14]

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 582984932-(7-chloro-6-fluoro-1H-benzimidazol-1-yl)ethanol

Product 1

HCID 58298447(7-chloro-6-fluoro-1H-benzimidazol-1-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 3776IsopropanolSolvent

Procedure

2-(7-Chloro-6-fluoro-1H-benzimidazol-1-yl)ethanol (550 mg, 2.57 mmol) is dissolved in AcOH (20.0 mL). Jones reagenta (3.31 mL, 3.00 mmol, 0.907 M) is added drop wise, and the solution is stirred for 1 hour at room temperature. The solution is diluted with iPrOH (50.0 mL), and the solvents are evaporated. 6N NaOH is added to the solution until the pH is 11. The aqueous phase is washed with EtOAc (50.0 mL), and the organic phase is extracted 3 times with water (3×50.0 mL). The combined aqueous phases are acidified with 12N HCl until the pH is 3. The aqueous phase is then extracted 4 times with EtOAc (4×50.0 mL). The combined organic phases are dried with MgSO4, filtered and concentrated. The product is sufficiently pure by 1H NMR (236 mg, 40%). 1H NMR (400 MHz, DMSO-D6) δ ppm 5.18 (s, 2H) 7.24 (dd, J=10.16, 8.79 Hz, 1H) 7.64 (dd, J=8.79, 4.49 Hz, 1H) 8.13-8.30 (m, 1H). a Jones reagent is prepared by mixing 997 mg of CrO3 in 1.00 mL of H2SO4 and 10.0 mL of water.

Workup

  1. additionJones reagenta (3.31 mL, 3.00 mmol, 0.907 M) is added drop wise
  2. customthe solvents are evaporated
  3. addition6N NaOH is added to the solution until the pH is 11
  4. washThe aqueous phase is washed with EtOAc (50.0 mL)
  5. extractionthe organic phase is extracted 3 times with water (3×50.0 mL)
  6. extractionThe aqueous phase is then extracted 4 times with EtOAc (4×50.0 mL)
  7. dry with materialThe combined organic phases are dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2e912b3f58ff40dcad023329d94e1485
Source dataset
uspto-grants-2011_03
Patent number
US07906654B2

Reaction notes

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