Citric Acid → HCID 18408321, compound

HRID 1385957Notes

Reaction equation

HRID 1385957 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10](=[O:21])[N:11]([CH3:20])[C:12]([C:16]([F:19])([F:18])[F:17])=[CH:13][C:14]=2[Cl:15])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:22][S:23](Cl)(=[O:25])=[O:24].C(N(CC)CC)C.[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C.CN(C=O)C.O.ClCCl>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[C:10](=[O:21])[N:11]([CH3:20])[C:12]([C:16]([F:19])([F:18])[F:17])=[CH:13][C:14]=2[Cl:15])=[CH:3][C:2]=1[NH:1][S:23]([CH3:22])(=[O:25])=[O:24]

Participants

10

Reactant 5

HCID 311Citric AcidHCID 8471TriethylamineHCID 14798Sodium Hydroxide2×HCID 31297Methanesulfonyl chlorideHCID 18408336HCID 18408336, compound

Product 1

HCID 18408321HCID 18408321, compoundYield 95.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To 20 ml of dichloromethane, 0.4 g (1.19 mmol) of 3-(3-amino-4-chlorophenyl)-4-chloro-1-methyl-6-trifluoromethyl-2(1H)-pyridone and 0.3 g (2.62 mmol) of methylsulfonyl chloride were dissolved, and 0.3 g (2.96 mmol) of triethylamine was added thereto under cooling with ice, followed by stirring at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into water and extracted with dichloromethane. The organic layer was washed with water and a 10% citric acid aqueous solution and dried over anhydrous magnesium sulfate. The organic layer was distilled off under reduced pressure, and the obtained crude crystals were dissolved in a mixed solvent comprising 15 ml of ethanol and 5 ml of DMF, and 3 ml of an aqueous sodium hydroxide solution [0.05 g (1.25 mmol) of sodium hydroxide] was added, followed by stirring at room temperature for 1 hour. After completion of the reaction, the reaction solution was poured into water and weakly acidified with citric acid and then extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The organic layer was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography to obtain 0.47 g (yield: 95%) of the desired product. Melting point: 161-163° C. 1H-NMR (400 MHz, CDCl3) δ value: 3.02(3H,s), 3.75(3H,s), 6.60(1H,s), 6.92(1H,s), 7.06(1H,dd), 7.26(1H,s), 7.47(1H,d), 7.59(1H,d)ppm.

Workup

  1. temperatureunder cooling with ice
  2. customAfter completion of the reaction
  3. extractionextracted with dichloromethane
  4. washThe organic layer was washed with water
  5. dry with materiala 10% citric acid aqueous solution and dried over anhydrous magnesium sulfate
  6. distillationThe organic layer was distilled off under reduced pressure
  7. customthe obtained crude crystals
  8. additionwas added
  9. stirringby stirring at room temperature for 1 hour
  10. customAfter completion of the reaction
  11. extractionextracted with ethyl acetate
  12. washThe organic layer was washed with water
  13. dry with materialdried over anhydrous magnesium sulfate
  14. distillationThe organic layer was distilled off under reduced pressure
  15. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-c18a84b195da45fe8e75848477c9906e
Source dataset
uspto-grants-2001_07
Patent number
US06265349B1

Reaction notes

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