Sodium Hydroxide → 4-(2-methyl-1H-imidazol-1-yl)benzoic acid

HRID 2367732Notes

Reaction equation

HRID 2367732 reaction equation
C[O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[CH:13][N:12]=[C:11]2[CH3:15])=[CH:6][CH:5]=1.[OH-].[Na+]>CO.O>[CH3:15][C:11]1[N:10]([C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:16])=[O:2])=[CH:5][CH:6]=2)[CH:14]=[CH:13][N:12]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 16413659HCID 16413659, compound

Product 1

HCID 138159884-(2-methyl-1H-imidazol-1-yl)benzoic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
-15 °C

Procedure

To a stirring solution of 4-(2-methyl-imidazol-1-yl)-benzoic acid methyl ester (250 mg) in MeOH (2 mL) add 10 M NaOH aqueous solution (2.3 mL) and stir the reaction at rt for 20 h. Dilute with water (25 mL) and cool to −15° C. Quench with careful dropwise addition of conc. HCl (2.2 mL) over 5 min to a final pH of 1-2. Wash the suspension with EtOAc (50 mL). Concentrate the aqueous layer to a solid, and further dry in vacuo under P2O5 to remove all moisture. Triturate the solid in MeOH and filter to remove inorganic salts, washing with MeOH. Concentrate the filtrate, triturate the residue in EtOAc/hexane, and filter, washing with hexane. Suspend the solid in 10% MeOH/EtOAc (20 mL) and stir/sonicate. Syringe filter the suspension to remove inorganics solids, concentrate the organic to a solid residue, and repeat this procedure. Triturate the organic residue in EtOAc/hexane and filter/dry the solid to afford the desired product 4-(2-methyl-imidazol-1-yl)-benzoic acid as a solid in 93% yield (238 mg, 1.06 mmol).

Workup

  1. customthe reaction at rt for 20 h
  2. customQuench with careful dropwise addition of conc. HCl (2.2 mL) over 5 min to a final pH of 1-2
  3. washWash the suspension with EtOAc (50 mL)
  4. concentrationConcentrate the aqueous layer to a solid
  5. customfurther dry in vacuo under P2O5
  6. customto remove all moisture
  7. customTriturate the solid in MeOH
  8. filtrationfilter
  9. customto remove inorganic salts
  10. washwashing with MeOH
  11. concentrationConcentrate the filtrate
  12. customtriturate the residue in EtOAc/hexane
  13. filtrationfilter
  14. washwashing with hexane
  15. customstir/sonicate
  16. filtrationSyringe filter the suspension
  17. customto remove inorganics solids
  18. concentrationconcentrate the organic to a solid residue
  19. customTriturate the organic residue in EtOAc/hexane
  20. customfilter/dry the solid

Sources & evidence

ORD record
ord-65eada8fa9fd47748f63d474256ffe01
Source dataset
uspto-grants-2014_04
Patent number
US08697911B2

Reaction notes

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