Hydrochloric Acid → Ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(2,4,6-trimethylbenzenesulfonyloxy)-1,8-naphthyridine-3-carboxylate

HRID 246956Notes

Reaction equation

HRID 246956 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:23]=[C:22]([O:24][S:25]([C:28]2[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=2[CH3:36])(=[O:27])=[O:26])[C:21]([F:37])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[O:13].[CH3:38]OC(OC)N(C)C.C(OC(=O)C)(=O)C.Cl.C(OC(C)C)(C)C>C(Cl)Cl.O.C(O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:10]2[C:11](=[CH:20][C:21]([F:37])=[C:22]([O:24][S:25]([C:28]3[C:33]([CH3:34])=[CH:32][C:31]([CH3:35])=[CH:30][C:29]=3[CH3:36])(=[O:26])=[O:27])[N:23]=2)[C:12](=[O:13])[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:38]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 7918Acetic AnhydrideHCID 78373Dimethylformamide dimethyl acetalHCID 13849317Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinoyl]acetate

Product 1

HCID 13849332Ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(2,4,6-trimethylbenzenesulfonyloxy)-1,8-naphthyridine-3-carboxylateYield 85.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

In 6 ml of methylene chloride was dissolved 300 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinoyl]acetate, and 135 mg of N,N-dimethylformamide dimethylacetal and 115 mg of acetic anhydride were added thereto, after which the resulting mixture was subjected to reaction at room temperature for 30 minutes. To the reaction mixture were added 0.31 ml of 2N hydrochloric acid and 3 ml of ethanol, and the resulting mixture was subjected to reaction at room temperature for 1 hour, after which 6 ml of methylene chloride and 6 ml of water were added thereto. The organic layer was separated, washed with 6 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 2 ml of diisopropyl ether, after which crystals were collected by filtration to obtain 260 mg (yield 85.1%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(2,4,6-trimethylbenzenesulfonyloxy)-1,8-naphthyridine-3-carboxylate having a melting point of 170°-173° C. The physical properties of this compound were identical with those of the compound obtained in Example 41.

Workup

  1. additionwere added
  2. customafter which the resulting mixture was subjected to reaction at room temperature for 30 minutes
  3. customthe resulting mixture was subjected to reaction at room temperature for 1 hour
  4. customThe organic layer was separated
  5. washwashed with 6 ml of saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed by distillation under reduced pressure
  8. customto the crystalline material thus obtained
  9. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-31086e3597df483cbf59f971050062a3
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

Loading…