Citric Acid → HCID 67490922, compound

HRID 1917425Notes

Reaction equation

HRID 1917425 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][C:14]([F:18])([F:17])[C@@H:13]1[CH2:12][N:11]([C:19]1[C:28]([CH3:29])=[C:27]3[C:22]([C:23](=[O:39])[C:24]([C:34]([O:36]CC)=[O:35])=[CH:25][N:26]3[C@@H:30]3[CH2:32][C@@H:31]3[F:33])=[CH:21][C:20]=1[F:40])[CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[C:1]([O:5][C:6]([NH:8][C@@:9]12[CH2:16][CH2:15][C:14]([F:17])([F:18])[C@@H:13]1[CH2:12][N:11]([C:19]1[C:28]([CH3:29])=[C:27]3[C:22]([C:23](=[O:39])[C:24]([C:34]([OH:36])=[O:35])=[CH:25][N:26]3[C@@H:30]3[CH2:32][C@@H:31]3[F:33])=[CH:21][C:20]=1[F:40])[CH2:10]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium Hydroxide2×HCID 67490962HCID 67490962, compound

Product 1

HCID 67490922HCID 67490922, compoundYield 82.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of ethyl 7-[(1S,5R)-1-tert-butoxycarbonylamino-6,6-difluoro-3-azabicyclo[3.3.0]octan-3-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylate (436 mg, 0.769 mmol) in ethanol (5 mL) was added 1 mol/L aqueous solution of sodium hydroxide (0.845 mL) at 0° C., and the mixture was stirred at room temperature for 13 hours. To the mixture was further added 1 mol/L aqueous solution of sodium hydroxide (0.845 mL) at 0° C., and the mixture was stirred at room temperature for 4 hours. To the mixture was added 10% aqueous solution of citric acid, and ethanol was distilled off under reduced pressure. The residue was diluted with water and extracted with dichloromethane (3×). The combined organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flush column chromatography (ethyl acetate/hexane=1:3→1:1→2:1→ethyl acetate) to afford 342 mg of the title compound as a colorless foam.

Workup

  1. customat 0° C.
  2. stirringthe mixture was stirred at room temperature for 4 hours
  3. distillationwas distilled off under reduced pressure
  4. additionThe residue was diluted with water
  5. extractionextracted with dichloromethane (3×)
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue was purified by silica gel
  9. customflush column chromatography (ethyl acetate/hexane=1:3→1:1→2:1→ethyl acetate)

Sources & evidence

ORD record
ord-541c86fcc68448d985e5d83101ee6921
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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