Toluene → Ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-methoxy-4-oxo-1,8-naphthyridine-3-carboxylate

HRID 232478Notes

Reaction equation

HRID 232478 reaction equation
[C:1]1(C)C=CC=CC=1.CN(C)C=O.S(OC)(OC)(=O)=O.C[O-].[Na+].[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[NH:31][C:32]1[N:45]=[C:44]([O:46][CH3:47])[C:43]([F:48])=[CH:42][C:33]=1[C:34]([CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])=[O:35]>C(OCC)C.O.C(OCC)(=O)C>[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[N:31]1[C:32]2[C:33](=[CH:42][C:43]([F:48])=[C:44]([O:46][CH3:47])[N:45]=2)[C:34](=[O:35])[C:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:1]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10942334Sodium MethoxideHCID 11127270DMF dimethylsulfateHCID 15596920Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate

Product 1

HCID 13849333Ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-methoxy-4-oxo-1,8-naphthyridine-3-carboxylateYield 82.8%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4 ml of toluene was added 540 mg of (N,N-dimethylformamide-dimethyl sulfate) complex compound, and 85 mg of sodium methoxide was added thereto at 0° C., after which the resulting mixture was subjected to reaction at 0° to 10° C. for 1 hour. Subsequently, 200 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate was further added to the reaction mixture, and the resulting mixture was subjected to reaction under reflux for 1.5 hours. The reaction mixture was added to a mixture of 8 ml of ethyl acetate and 8 ml of water, and the organic layer was separated, washed with 5 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 1 ml of diethyl ether, after which crystals were collected by filtration to obtain 170 mg (yield 82.8%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-methoxy-4-oxo-1,8-naphthyridine-3-carboxylate. The physical properties of this compound were identical with those of the compound obtained in Example 41.

Workup

  1. additionwas added
  2. customat 0° C., after which the resulting mixture was subjected to reaction at 0° to 10° C. for 1 hour
  3. customthe resulting mixture was subjected to reaction
  4. temperatureunder reflux for 1.5 hours
  5. customthe organic layer was separated
  6. washwashed with 5 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-27319b894ed4426e9363508701696bba
Source dataset
uspto-grants-1989_07
Patent number
US04851535

Reaction notes

Loading…