Hydrochloric Acid → 3-Pyridinecarboxylic acid,2-[(2,4-difluorophenyl)amino]-5-fluoro-6-methoxy-

HRID 246935Notes

Reaction equation

HRID 246935 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]([O:20][CH3:21])[C:17]([F:22])=[CH:16][C:11]=1[C:12]([O:14]C)=[O:13].[OH-].[Na+].C(OCC)(=O)C.Cl>O1CCCC1.C(OCC)C.O>[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][CH3:21])[C:17]([F:22])=[CH:16][C:11]=1[C:12]([OH:14])=[O:13]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 13821754Methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinate

Product 1

HCID 138217673-Pyridinecarboxylic acid,2-[(2,4-difluorophenyl)amino]-5-fluoro-6-methoxy-Yield 73.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

In 60 ml of tetrahydrofuran was dissolved 2.00 g of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinate, and 25.5 ml of 1N aqueous sodium hydroxide solution was added thereto at room temperature, after which the resulting mixture was subjected to reaction under reflux for 7 hours. Subsequently, the solvent was removed by distillation under reduced pressure, and to the residue thus obtained were added 100 ml of ethyl acetate and 100 ml of water, after which the pH of the resulting mixture was adjusted to 2.0 with 2N hydrochloric acid. The organic layer was washed successively with 50 ml of water and 50 ml of saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 10 ml of diethyl ether, after which crystals were collected by filtration to obtain 1.40 g (yield 73.3%) of 2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinic acid having a melting point of 237°-240° C.

Workup

  1. additionwas added
  2. customat room temperature, after which the resulting mixture was subjected to reaction
  3. temperatureunder reflux for 7 hours
  4. customSubsequently, the solvent was removed by distillation under reduced pressure
  5. customto the residue thus obtained
  6. washThe organic layer was washed successively with 50 ml of water and 50 ml of saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was removed by distillation under reduced pressure
  9. customto the crystalline material thus obtained
  10. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-878e011fcfb84635aa34eaeaa2a94673
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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