Potassium tert-butoxide → 6-Bromo-4-fluoro-2-methyl-1-(propan-2-yl)-1H-benzimidazole

HRID 2264373Notes

Reaction equation

HRID 2264373 reaction equation
CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]([NH:15][C:16](=[N:18][CH:19]([CH3:21])[CH3:20])[CH3:17])=[C:10](F)[CH:9]=1>CNC=O>[Br:7][C:8]1[CH:13]=[C:12]([F:14])[C:11]2[N:15]=[C:16]([CH3:17])[N:18]([CH:19]([CH3:21])[CH3:20])[C:10]=2[CH:9]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 674267372177297-18-4

Product 1

HCID 569716626-Bromo-4-fluoro-2-methyl-1-(propan-2-yl)-1H-benzimidazoleYield 72.9%

Reagents, catalysts & solvents 1

HCID 31254N-MethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

Add potassium tert-butoxide (6.9 kg) in portions to a solution of N-(4-bromo-2,6-difluoro-phenyl)-N′-isopropyl-acetamidine (16.2 kg) in N-methyl formamide (76 kg) while maintaining the temperature at T<30° C. Heat the mixture at 70-75° C. until complete by HPLC. Cool to 20-30° C. and quench by adding into water (227 kg) then extract with MtBE (37×4 kg). Wash the combined organic phases with brine (49×2 kg) and concentrate to 25-30 L, add n-hexane (64 kg) and filter the slurry to give 11 kg of the title compound. MS (ES+): m/z=272 (M+H)+.

Workup

  1. temperatureHeat the mixture at 70-75° C. until complete by HPLC
  2. temperatureCool to 20-30° C.
  3. customquench
  4. additionby adding into water (227 kg)
  5. extractionthen extract with MtBE (37×4 kg)
  6. washWash the combined organic phases with brine (49×2 kg)
  7. concentrationconcentrate to 25-30 L
  8. additionadd n-hexane (64 kg)
  9. filtrationfilter the slurry

Sources & evidence

ORD record
ord-521327eff4b242749b88a137212eb609
Source dataset
uspto-grants-2010_12
Patent number
US07855211B2

Reaction notes

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