Methanesulfonic Acid → HCID 23299447, compound

HRID 1952729Notes

Reaction equation

HRID 1952729 reaction equation
CS(O)(=O)=O.[NH2:6][C:7]1[N:11]([S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])[C:10]2[CH:18]=[C:19]([C:22]([C:25]3[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=3[F:32])([CH3:24])O)[CH:20]=[CH:21][C:9]=2[N:8]=1.C(=O)(O)[O-].[Na+].[OH-].[Na+]>C(Cl)Cl>[CH:15]([S:12]([N:11]1[C:10]2[CH:18]=[C:19]([C:22]([C:25]3[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:26]=3[F:32])=[CH2:24])[CH:20]=[CH:21][C:9]=2[N:8]=[C:7]1[NH2:6])(=[O:13])=[O:14])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 23299452HCID 23299452, compound

Product 1

HCID 23299447HCID 23299447, compoundYield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonic acid (33.0 g, 344 mmol) was added to a solution of 2-amino-α-(2,5-difluorophenyl)-α-methyl-1-[(1-methylethyl)sulfonyl]benzimidazole-6-methanol (53.4 g, 97% purity, 115 mmol) in methylene chloride (500 mL) and the solution turned from beige to brown. The solution was heated at reflux for 1.5 hours until the reaction was complete. After cooling to room temperature, a saturated aqueous solution of sodium bicarbonate (200 mL) was added to neutralize the acid. However, the pH remained at 1 and extensive foaming occurred. The reaction mixture was then neutralized to pH 7-8 with 1N sodium hydroxide (about 90 mL) while keeping the temperature at 20° C. The phases were separated and the organic phase extracted with methylene chloride (100 mL). The combined organic fractions were washed with brine (100 mL) and dried over sodium sulfate. The hazy mixture was filtered to give a clear burnt-orange solution which was concentrated by rotary evaporation at 40-70° C. to give 39.9 g of the title compound as a beige powder (98.5% purity, 91% yield), mp 161.0-164.5° C.

Workup

  1. temperatureThe solution was heated
  2. temperatureat reflux for 1.5 hours until the reaction
  3. customat 20° C
  4. customThe phases were separated
  5. extractionthe organic phase extracted with methylene chloride (100 mL)
  6. washThe combined organic fractions were washed with brine (100 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationThe hazy mixture was filtered
  9. customto give a clear burnt-orange solution which
  10. concentrationwas concentrated by rotary evaporation at 40-70° C.

Sources & evidence

ORD record
ord-c02489eeaa304e989c4883330c520ce8
Source dataset
uspto-grants-2000_09
Patent number
US06114327

Reaction notes

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