Hydrochloric Acid → HCID 19072265, compound

HRID 1955758Notes

Reaction equation

HRID 1955758 reaction equation
[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])(C)C)(=[O:12])[CH2:4][C:5]([O:7]C(C)(C)C)=O.[CH:18]1([N:21]2[C:30]3[C:25](=[CH:26][C:27]([F:34])=[C:28](F)[C:29]=3[O:31][CH3:32])C(=O)C(=O)[CH:22]2C(OCC)=O)[CH2:20][CH2:19]1.Cl.F[C:44](F)(F)[C:45]([OH:47])=[O:46].[C:50]1([C:56]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)=[N+]=[N-])[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.ClCCl.C1(C(C2C=CC=CC=2)=[N+]=[N-])C=CC=CC=1>C(Cl)Cl.CO.C(O)(=O)C.O.C(OCC)(=O)C.CN(C)C=O>[CH:18]1([N:21]2[C:30]3[C:25](=[CH:26][C:27]([F:34])=[C:28]([CH2:44][C:45]([O:47][CH:56]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=4)=[O:46])[C:29]=3[O:31][CH3:32])[C:5](=[O:7])[C:4]([C:3]([O:13][CH2:14][CH3:17])=[O:12])=[CH:22]2)[CH2:19][CH2:20]1

Participants

14

Reactant 7

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 612301,1'-(Diazomethylene)bis(benzene)HCID 68324Di-tert-butyl malonateHCID 69221498HCID 69221498, compoundHCID 86752891HCID 86752891, compound

Product 1

HCID 19072265HCID 19072265, compoundYield 59%

Reagents, catalysts & solvents 6

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

30.7 g of sodium hydride was suspended in 1.8 1 of N,N-dimethylformamide and 261 g of di-t-butyl malonate was dropped thereinto over 2 hours under ice-cooling. After the completion of the addition, 100 g of ethyl 1-cyclo-propyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolone-carboxylate was added thereto. Then the mixture was stirred successively at 50° to 60° C. for 3 hours, at room temperature for 12.5 hours, at 50° to 60° C. for 11 hours and at room temperature for 14 hours. Next, conc. hydrochloric acid was added thereto under ice-cooling to thereby regulate the pH value of the mixture to 1. After adding ethyl acetate and water, the organic layer was collected, successively washed with water and a saturated aqueous solution of sodium hydro-gencarbonate and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, diisopropyl ether was added to the obtained residue and the solid thus precipitated was collected by filtration. To the solid thus obtained, 500 ml of methylene chloride and 500 ml of tri-fluoroacetic acid were added. Then the mixture was stirred at room temperature for 66 hours. After removing the solvent under reduced pressure, diethyl ether was added to the obtained residue and the solid thus precipitated was collected by filtration. The solid thus obtained was suspended in 700 ml of methylene chloride and 300 ml of methanol. Then a diphenyldiazomethane-dichloromethane solution was dropped thereinto until the color of the mixture did not fade any more. Then the excessive diphenyldiazomethane was decomposed with acetic acid and the solvent was removed under reduced pressure. To the obtained residue, diethyl ether was added. The solid thus precipitated was collected by filtration. Thus 96.7 g of ethyl 1-cyclopropyl-7-diphenylmethoxycarbonylmethyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylate was obtained (yield: 59.0%).

Workup

  1. additionwas dropped
  2. temperatureover 2 hours under ice-cooling
  3. additionwas added
  4. temperatureunder ice-cooling
  5. customthe organic layer was collected
  6. washsuccessively washed with water
  7. dry with materiala saturated aqueous solution of sodium hydro-gencarbonate and dried over anhydrous sodium sulfate
  8. customAfter removing the solvent under reduced pressure, diisopropyl ether
  9. additionwas added to the obtained residue
  10. customthe solid thus precipitated
  11. filtrationwas collected by filtration
  12. customTo the solid thus obtained
  13. stirringThen the mixture was stirred at room temperature for 66 hours
  14. customAfter removing the solvent under reduced pressure, diethyl ether
  15. additionwas added to the obtained residue
  16. customthe solid thus precipitated
  17. filtrationwas collected by filtration
  18. customThe solid thus obtained
  19. customthe solvent was removed under reduced pressure
  20. additionTo the obtained residue, diethyl ether was added
  21. customThe solid thus precipitated
  22. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-de98209be7d6470c852783a12d449192
Source dataset
uspto-grants-1998_07
Patent number
US05776948

Reaction notes

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