Hydrochloric Acid → 364069-13-6

HRID 2183687Notes

Reaction equation

HRID 2183687 reaction equation
[NH2:1][C@H:2]1[C:6]2([CH2:8][CH2:7]2)[CH2:5][N:4]([C:9]2[C:18]([O:19][CH3:20])=[C:17]3[C:12]([C:13](=[O:28])[C:14]([C:25]([OH:27])=[O:26])=[CH:15][N:16]3[C@@H:21]3[CH2:23][C@@H:22]3[F:24])=[CH:11][C:10]=2[F:29])[CH2:3]1.[ClH:30]>CC(O)C>[OH2:19].[ClH:30].[NH2:1][C@H:2]1[C:6]2([CH2:7][CH2:8]2)[CH2:5][N:4]([C:9]2[C:18]([O:19][CH3:20])=[C:17]3[C:12]([C:13](=[O:28])[C:14]([C:25]([OH:27])=[O:26])=[CH:15][N:16]3[C@@H:21]3[CH2:23][C@@H:22]3[F:24])=[CH:11][C:10]=2[F:29])[CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 5271826364069-14-7

Product 1

HCID 9955877364069-13-6Yield 82.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

In a 3-liter teardrop flask, crystalline (−)-7-[(7S)-7-amino-5-azaspiro[2.4]heptan-5-yl]-6-fluoro-1-[(1R, 2S)-2-fluoro-1-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid 0.5 hydrate (61.3 g; 148 mmol: calculated based on the free form: 60.0 g) was suspended in 2-propanol (720 ml). Subsequently, hydrochloric acid (5N: 59.2 ml; 296 mmol) was slowly added dropwise to the suspension while being stirred under ice cooling. The thus-obtained mixture was brought to room temperature, and distilled water (420 ml) was added thereto, followed by stirring for 10 minutes. The mixture was heated to 60° C. in a water bath while being stirred. After the suspension turned into a transparent solution, activated carbon (3 g) was added thereto, and the admixture was stirred for 20 minutes at an external temperature of 80° C. The activated carbon was filtered off, and the filtrate was concentrated under reduced pressure, followed by concentrated to driness through evaporation. The residue was dried in a water bath at 70° C. for 1 hour by use of a vacuum pump, and 2-propanol (96%: 1800 ml) was added thereto, followed by stirring in a water bath at 80° C. After a homogenous (clear) solution was obtained, the solution was stirred at 60° C. After a while, crystals began to precipitate, when the temperature of the water bath was brought to 25° C. over about 1.5 hours, followed by slow stirring for 20 hours. Crystals that precipitated were collected by filtration, washed with 2-propanol, and dried under reduced pressure at 70° C., to thereby yield 56.3 g of the title compound as pale yellow crystals (yield: 82.7%).

Workup

  1. customwas brought to room temperature
  2. distillationdistilled water (420 ml)
  3. additionwas added
  4. stirringby stirring for 10 minutes
  5. stirringwhile being stirred
  6. additionwas added
  7. stirringthe admixture was stirred for 20 minutes at an external temperature of 80° C
  8. filtrationThe activated carbon was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. concentrationby concentrated to driness through evaporation
  11. dry with materialThe residue was dried in a water bath at 70° C. for 1 hour by use of a vacuum pump, and 2-propanol (96%: 1800 ml)
  12. additionwas added
  13. stirringby stirring in a water bath at 80° C
  14. customAfter a homogenous (clear) solution was obtained
  15. stirringthe solution was stirred at 60° C
  16. customto precipitate
  17. stirringby slow stirring for 20 hours
  18. customCrystals that precipitated
  19. filtrationwere collected by filtration
  20. washwashed with 2-propanol
  21. customdried under reduced pressure at 70° C.

Sources & evidence

ORD record
ord-d46434fef02e41c6915d26a793f57da9
Source dataset
uspto-grants-2005_05
Patent number
US06900225B2

Reaction notes

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