Hydrochloric Acid → 7-[(3S,4S)-3-(tert-Butoxycarbonyl)amino-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid

HRID 1010572Notes

Reaction equation

HRID 1010572 reaction equation
[OH-].[Na+].[C:3]([O:7][C:8]([NH:10][C@H:11]1[C@@H:15]([CH3:16])[CH2:14][N:13]([C:17]2[CH:26]=[C:25]3[C:20]([C:21](=[O:35])[C:22]([C:30]([O:32]CC)=[O:31])=[CH:23][N:24]3[CH:27]3[CH2:29][CH2:28]3)=[CH:19][C:18]=2[F:36])[CH2:12]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl>C(O)C>[C:3]([O:7][C:8]([NH:10][C@H:11]1[C@@H:15]([CH3:16])[CH2:14][N:13]([C:17]2[CH:26]=[C:25]3[C:20]([C:21](=[O:35])[C:22]([C:30]([OH:32])=[O:31])=[CH:23][N:24]3[CH:27]3[CH2:29][CH2:28]3)=[CH:19][C:18]=2[F:36])[CH2:12]1)=[O:9])([CH3:4])([CH3:5])[CH3:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 67308688Ethyl 7-[(3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate

Product 1

HCID 673087927-[(3S,4S)-3-(tert-Butoxycarbonyl)amino-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acidYield 58.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A 1 mol/L aqueous sodium hydroxide solution (5 mL, 5 mmol) was added under cooling with ice to ethyl 7-[(3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate (957 mg, 1.96 mmol) in ethanol (10 mL), and the mixture was stirred at room temperature for 3 hours. The resultant mixture was neutralized with 1 mol/L hydrochloric acid under cooling with ice, and ethanol was removed under reduced pressure. Subsequently, 1 mol/L hydrochloric acid was added thereto, followed by extraction with ethyl acetate (100 mL×3). The ethyl acetate layer was washed by saturated brine (100 mL), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in concentrated hydrochloric acid (5 mL), and the solution was washed by chloroform (50 mL). The pH of the resultant mixture was adjusted to 7.8 with an aqueous sodium hydroxide solution, followed by extraction with chloroform (100 mL×3) and drying over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was recrystallized from ethanol, to thereby yield the title compound as pale yellow crystals (420 mg, 58.2%).

Workup

  1. customwas removed under reduced pressure
  2. additionSubsequently, 1 mol/L hydrochloric acid was added
  3. extractionfollowed by extraction with ethyl acetate (100 mL×3)
  4. washThe ethyl acetate layer was washed by saturated brine (100 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. dissolutionThe obtained residue was dissolved in concentrated hydrochloric acid (5 mL)
  9. washthe solution was washed by chloroform (50 mL)
  10. extractionfollowed by extraction with chloroform (100 mL×3)
  11. dry with materialdrying over anhydrous sodium sulfate
  12. filtrationAfter filtration
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customthe obtained residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-b10f7604527949a6b2add64aba898e37
Source dataset
uspto-grants-2011_07
Patent number
US07977327B2

Reaction notes

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