Citric Acid → HCID 69138135, compound

HRID 1458014Notes

Reaction equation

HRID 1458014 reaction equation
C(O[C:9]([N:11]1[CH2:15][CH2:14][C@H:13]([C:16]2(CNC(OC(C)(C)C)=O)[CH2:18][CH2:17]2)[CH2:12]1)=O)C1C=CC=CC=1.[H][H].[F:30][C:31]1[C:32]([OH:51])=[C:33]2[C:38](=[C:39]([F:42])C=1F)[N:37]([C@@H:43]1[CH2:45][C@@H:44]1[F:46])[CH:36]=[C:35]([C:47]([OH:49])=[O:48])[C:34]2=[O:50].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[OH-].[Na+].C(#[N:69])C>CO.[C].[Pd].C(N(CC)CC)C>[NH2:69][C:16]1([C@@H:13]2[CH2:14][CH2:15][N:11]([C:9]3[C:39]([F:42])=[C:38]4[C:33]([C:34](=[O:50])[C:35]([C:47]([OH:49])=[O:48])=[CH:36][N:37]4[C@@H:43]4[CH2:45][C@@H:44]4[F:46])=[C:32]([OH:51])[C:31]=3[F:30])[CH2:12]2)[CH2:17][CH2:18]1

Participants

10

Reactant 6

HCID 311Citric AcidHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 53958710HCID 53958710, compoundHCID 69139892HCID 69139892, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 69138135HCID 69138135, compoundYield 82%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolventHCID 8471TriethylamineSolvent

Procedure

A 360 mg (1.00 mmol) portion of (R)-1-benzyloxycarbonyl-3-(1-tert-butoxycarbonylaminomethylcyclopropyl)pyrrolidine was dissolved in 10 ml of methanol to which was subsequently added 125 mg of 5% (v/v) palladium-carbon to carry out 3.5 hours of stirring at room temperature in a stream of hydrogen. After filtration through celite, methanol was evaporated. The resulting residue was mixed with 1 ml of triethylamine and 159 mg (0.50 mmol) of 6,7,8-trifluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-5-hydroxy-4-oxoquinoline-3-carboxylic acid which has been dissolved in 10 ml of acetonitrile, and the thus prepared mixture was heated under reflux for 1 hour. After completion of the reaction, the reaction solution was mixed with 10% citric acid and extracted with chloroform (50 ml×3). The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. A 5 ml portion of concentrated hydrochloric acid was added dropwise to the resulting residue, followed by 1.5 hours of stirring at room temperature. After completion of the reaction, the reaction solution was adjusted to pH 12 with sodium hydroxide aqueous solution and then to pH 7.4 with hydrochloric acid, and the thus precipitated crystals were collected by filtration. The resulting filtrate was extracted with chloroform (100 ml×3). The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. Thereafter, the resulting residue and the collected crystals were combined, and recrystallized from ethanol-liquid ammonia to yield 227 mg (82%) of the title compound.

Workup

  1. filtrationAfter filtration through celite, methanol
  2. customwas evaporated
  3. temperaturethe thus prepared mixture was heated
  4. temperatureunder reflux for 1 hour
  5. customAfter completion of the reaction
  6. extractionextracted with chloroform (50 ml×3)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. customthe solvent was evaporated
  9. additionA 5 ml portion of concentrated hydrochloric acid was added dropwise to the resulting residue
  10. waitfollowed by 1.5 hours
  11. customAfter completion of the reaction
  12. filtrationto pH 7.4 with hydrochloric acid, and the thus precipitated crystals were collected by filtration
  13. extractionThe resulting filtrate was extracted with chloroform (100 ml×3)
  14. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  15. customthe solvent was evaporated
  16. customrecrystallized from ethanol-liquid ammonia

Sources & evidence

ORD record
ord-eff7a5b3a0eb458b8dd42d59b85cd48c
Source dataset
uspto-grants-1998_12
Patent number
US05849757

Reaction notes

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