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 246958Notes

Reaction equation

HRID 246958 reaction equation
[CH3:1]N(C)C=O.S(OC)(OC)(=O)=O.C[O-].[Na+].[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[NH:24][C:25]1[N:38]=[C:37]([O:39][S:40]([C:43]2[C:48]([CH3:49])=[CH:47][C:46]([CH3:50])=[CH:45][C:44]=2[CH3:51])(=[O:42])=[O:41])[C:36]([F:52])=[CH:35][C:26]=1[C:27]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:28].C(OC(=O)C)(=O)C.Cl.C(OC(C)C)(C)C>O.C(Cl)Cl.C(O)C>[F:16][C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[N:24]1[C:25]2[C:26](=[CH:35][C:36]([F:52])=[C:37]([O:39][S:40]([C:43]3[C:48]([CH3:49])=[CH:47][C:46]([CH3:50])=[CH:45][C:44]=3[CH3:51])(=[O:41])=[O:42])[N:38]=2)[C:27](=[O:28])[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:1]1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 7918Acetic AnhydrideHCID 10942334Sodium MethoxideHCID 11127270DMF dimethylsulfateHCID 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 80.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 6 ml of methylene chloride was added 335 mg of (N,N-dimethylformamide-dimethyl sulfate) complex compound, and 65 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, 300 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-trimethylbenzenesulfonyloxy)nicotinoyl]acetate and 115 mg of acetic anhydride were added thereto. The resulting mixture was subjected to reaction at room temperature for 2 hours, and 0.31 ml of 2N hydrochloric acid and 3 ml of ethanol were added to the reaction mixture, after which the resulting mixture was subjected to reaction at room temperature for 1.5 hours. The reaction mixture was added to a mixture of 6 ml of methylene chloride and 6 ml of water, and 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 245 mg (yield 80.2%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(2,4,6-trimethylbenzenesulfonyloxy)-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 at room temperature for 2 hours
  4. customafter which the resulting mixture was subjected to reaction at room temperature for 1.5 hours
  5. customthe organic layer was separated
  6. washwashed with 6 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-79878201a5e94b5e8240f26352d0c062
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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