Hydrochloric Acid → 3-(4-Chloro-2-fluoro-5-methoxyphenyl)-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine

HRID 849959Notes

Reaction equation

HRID 849959 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[CH:8](Br)[C:9]([C:11]([F:14])([F:13])[F:12])=O.[NH2:16][CH:17]([C:21]1[CH:26]=[C:25]([O:27][CH3:28])[C:24]([Cl:29])=[CH:23][C:22]=1[F:30])[C:18]([NH2:20])=[O:19].Cl>O>[Cl:29][C:24]1[C:25]([O:27][CH3:28])=[CH:26][C:21]([C:17]2[C:18](=[O:19])[NH:20][C:9]([C:11]([F:14])([F:13])[F:12])=[CH:8][N:16]=2)=[C:22]([F:30])[CH:23]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 5505231,1-Dibromo-3,3,3-trifluoroacetoneHCID 193655102-Amino-2-(4-chloro-2-fluoro-5-methoxyphenyl)acetamide

Product 1

HCID 154520793-(4-Chloro-2-fluoro-5-methoxyphenyl)-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a mixed solution of 17.2 g of sodium carbonate and 61 ml of water was added dropwise 10.9 g of 1,1-dibromo-3,3,3-trifluoroacetone at such a rate that the temperature of the reaction mixture became not higher than 55° C. After completion of the dropwise addition, the mixture was stirred at room temperature for 30 minutes, followed by adding 84 ml of water and then 7.10 g of 2-amino-2-(4-chloro-2-fluoro-5-methoxyphenyl)acetamide, and the reaction was allowed to proceed at 60° C. for 2 hours. After completion of the reaction, the reaction mixture was cooled to 10° C. or lower, made acidic by adding 9.2 ml of concentrated hydrochloric acid at the same temperature, and extracted with ethyl acetate. The organic layer was washed with water and then saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane/ethyl acetate=4:1), which afforded 3.61 g (yield, 37%) of the desired compound, 3-(4-chloro-2-fluoro-5-methoxyphenyl)-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (compound 1-1008).

Workup

  1. custombecame not higher than 55° C
  2. additionAfter completion of the dropwise addition
  3. waitto proceed at 60° C. for 2 hours
  4. customAfter completion of the reaction
  5. temperaturethe reaction mixture was cooled to 10° C.
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with water
  8. dry with materialsaturated sodium chloride solution, dried with anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customafforded

Sources & evidence

ORD record
ord-4e01c20971f4402484110dda1c9cb93e
Source dataset
uspto-grants-2000_01
Patent number
US06015774

Reaction notes

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