Water → Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinate

HRID 232448Notes

Reaction equation

HRID 232448 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:19]=[C:18]([OH:20])[C:17]([F:21])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[O:13].[C:22](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O.O>CN(C)C=O.C(O)(C)C.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:19]=[C:18]([O:20][CH3:22])[C:17]([F:21])=[CH:16][C:11]=1[C:12]([O:14][CH3:15])=[O:13]

Participants

8

Reactant 4

HCID 962WaterHCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 178498343Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate

Product 1

HCID 13821754Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinateYield 86%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 5 ml of N,N-dimethylformamide was dissolved 200 mg of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate, and to the resulting solution were added 110 mg of potassium carbonate and 93 mg of dimethyl sulfate at room temperature, after which the resulting mixture was subjected to reaction at the same temperature for 2 hours. Subsequently, 20 ml of water and 20 ml of ethyl acetate were added to the reaction mixture, and the organic layer was then separated, washed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution, and thereafter dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 5 ml of isopropyl alcohol, after which crystals were collected by filtration to obtain 180 mg (yield 86.0%) of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinate. The physical properties of this compound were identical with those of the compound obtained in Example 2.

Workup

  1. customafter which the resulting mixture was subjected to reaction at the same temperature for 2 hours
  2. customthe organic layer was then separated
  3. washwashed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was removed by distillation under reduced pressure
  6. customto the crystalline material thus obtained
  7. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-f31723e0d67c43e184d4e03a4ed6ae0a
Source dataset
uspto-grants-1989_07
Patent number
US04851535

Reaction notes

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