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

HRID 246962Notes

Reaction equation

HRID 246962 reaction equation
[CH3:1]N(C)C=O.P(Cl)(Cl)(Cl)=O.[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[NH:19][C:20]1[N:33]=C(OC)[C:31]([F:36])=[CH:30][C:21]=1[C:22]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[O:23].O.[CH:38]([Cl:41])(Cl)Cl>C(OCC)C>[Cl:41][C:38]1[N:33]=[C:20]2[C:21]([C:22](=[O:23])[C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:1][N:19]2[C:13]2[CH:14]=[CH:15][C:16]([F:18])=[CH:17][C:12]=2[F:11])=[CH:30][C:31]=1[F:36]

Participants

7

Reactant 5

HCID 962WaterHCID 6212ChloroformHCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 15596920Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate

Product 1

HCID 1268243Ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylateYield 72.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Into 4 ml of N,N-dimethylformamide was dropped 250 mg of phosphorus oxychloride with ice-cooling, and 200 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate was added thereto after stirring at the same temperature for 10 minutes. The resulting mixture was subjected to reaction at 50° to 60° C. for 3.5 hours. The reaction mixture was poured into 50 ml of iced water, and 20 ml of chloroform was added thereto, after which the organic layer was separated, washed with 20 ml of water, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the residue thus obtained was added 5 ml of diethyl ether, after which crystals were collected by filtration to obtain 150 mg (yield 72.2%) of ethyl 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate having a melting point of 217°-220° C. This was recrystallized from an acetone-methanol mixture (1:1 by volume) to obtain crystals having a melting point of 219°-221° C.

Workup

  1. temperaturecooling
  2. customThe resulting mixture was subjected to reaction at 50° to 60° C. for 3.5 hours
  3. additionwas added
  4. customafter which the organic layer was separated
  5. washwashed with 20 ml of water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure
  8. customto the residue thus obtained
  9. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-aafbe01e93a940648b300c4bd74111fc
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

Loading…