Citric Acid → HCID 15457057, compound

HRID 992873Notes

Reaction equation

HRID 992873 reaction equation
[NH2:1][C:2]1[C:3]([Cl:21])=[CH:4][C:5]([F:20])=[C:6]([C:8]2[C:9](=[O:19])[N:10]([CH3:18])[C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=2)[CH:7]=1.C(N(CC)CC)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.[Cl-].[NH4+].C(O)C.O>[Cl:21][C:3]1[C:2]([NH:1][S:30]([CH3:29])(=[O:32])=[O:31])=[CH:7][C:6]([C:8]2[C:9](=[O:19])[N:10]([CH3:18])[C:11]([C:14]([F:17])([F:15])[F:16])=[CH:12][CH:13]=2)=[C:5]([F:20])[CH:4]=1

Participants

10

Reactant 5

HCID 311Citric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 15457056HCID 15457056, compound

Product 1

HCID 15457057HCID 15457057, compoundYield 72%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

0.9 g (2.8 mmol) of 3-(5-amino-4-chloro-2-fluorophenyl)-1-methyl-6-trifluoromethyl-2(1H)-pyridone and 0.6 g (5.9 mmol) of triethylamine were dissolved in 20 ml of dichloromethane, and 0.7 g (6.1 mmol) of methylsulfonyl chloride was dropwise added thereto under cooling with ice. The mixture was stirred at room temperature for 2 hours and then diluted with an aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate. After washing with water and a saturated sodium chloride aqueous solution, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure. Then, the obtained crude crystals of the bissulfone compound were dissolved in 25 ml of ethanol, and 10 ml (5.0 mmol) of a 0.5N sodium hydroxide aqueous solution was added at room temperature, followed by stirring for 1 hour. The mixture was poured into water, acidified with citric acid and extracted with ethyl acetate. After washing with water, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure. Then, the obtained crude crystals were washed with n-hexane to obtain 0.80 g (yield: 72%) of the desired product. Melting point: 113-114° C.

Workup

  1. temperatureunder cooling with ice
  2. extractionThe mixture was extracted with ethyl acetate
  3. washAfter washing with water
  4. dry with materiala saturated sodium chloride aqueous solution, the organic layer was dried over anhydrous magnesium sulfate
  5. distillationEthyl acetate was distilled off under reduced pressure
  6. customThen, the obtained crude crystals of the bissulfone compound
  7. stirringby stirring for 1 hour
  8. extractionextracted with ethyl acetate
  9. washAfter washing with water
  10. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  11. distillationEthyl acetate was distilled off under reduced pressure
  12. customThen, the obtained crude crystals
  13. washwere washed with n-hexane

Sources & evidence

ORD record
ord-542317968eb94901a66ff1c6d82fd600
Source dataset
uspto-grants-2002_10
Patent number
US06472348B1

Reaction notes

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