Acetic Acid → 5-Amino-1-cyclopropyl-8-difluoromethoxy-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 2356379Notes

Reaction equation

HRID 2356379 reaction equation
O.C(O)(=O)C.[CH:6]1([N:9]2[C:18]3[C:13](=[C:14]([N+:25]([O-])=O)[C:15]([F:24])=[C:16]([F:23])[C:17]=3[O:19][CH:20]([F:22])[F:21])[C:12](=[O:28])[C:11]([C:29]([O:31]CC)=[O:30])=[CH:10]2)[CH2:8][CH2:7]1>[Fe].C(O)C>[NH2:25][C:14]1[C:15]([F:24])=[C:16]([F:23])[C:17]([O:19][CH:20]([F:21])[F:22])=[C:18]2[C:13]=1[C:12](=[O:28])[C:11]([C:29]([OH:31])=[O:30])=[CH:10][N:9]2[CH:6]1[CH2:8][CH2:7]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 15023843Ethyl 1-cyclopropyl-8-difluoromethoxy-6,7-difluoro-5-nitro-1,4-dihydro-4-oxoquinoline-3-carboxylate

Product 1

HCID 150238455-Amino-1-cyclopropyl-8-difluoromethoxy-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 84.5%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

The preparation comprises refluxing mixture of reducing iron powder (2.4 g, 42.8 mmol), water (4.5 mL) and acetic acid (0.3 mL) for 15 min under stirring, adding batch-wise ethyl 1-cyclopropyl-6,7-difluoro-8-difluoromethoxyl-5-nitro-1,4-dihydro-4-oxoquinoline-3-carboxylate (4.3 g, 10.6 mmol), adding ethanol (20 mL), continuously refluxing for 6 h under stirring, hot filtering, distilling off the solvent from the filtrate, adding concentrated hydrochloric acid (5 mL) and acetic acid (10 mL) to react at 100° C. for 1 h, cooling to room temperature, filtering, adding ethanol (10 mL) to the filter cake to reflux for 0.5 h, cooling to room temperature, filtering, and drying obtained filter cake to give a pale yellow solid product 5-amino-1-cyclopropyl-6,7-difluoro-8-difluoromethoxyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (3.1 g, 84.5%).

Workup

  1. temperatureThe preparation comprises refluxing
  2. temperaturecontinuously refluxing for 6 h
  3. stirringunder stirring
  4. distillationhot filtering, distilling off the solvent from the filtrate
  5. additionadding concentrated hydrochloric acid (5 mL) and acetic acid (10 mL)
  6. customto react at 100° C. for 1 h
  7. filtrationfiltering
  8. additionadding ethanol (10 mL) to the filter cake
  9. temperatureto reflux for 0.5 h
  10. temperaturecooling to room temperature
  11. filtrationfiltering
  12. customdrying
  13. customobtained
  14. filtrationfilter cake

Sources & evidence

ORD record
ord-8935983cfb6741f99c8057e72c8ba50d
Source dataset
uspto-grants-2010_07
Patent number
US07759362B2

Reaction notes

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