Isopropanol → HCID 71570094, compound

HRID 1528027Notes

Reaction equation

HRID 1528027 reaction equation
[ClH:1].[CH:2]1([NH:5][CH2:6][C@@H:7]2[C@H:11]([F:12])[CH2:10][N:9]([C:13]3[C:22]([O:23][CH3:24])=[C:21]4[C:16]([C:17](=[O:31])[C:18]([C:28]([OH:30])=[O:29])=[CH:19][N:20]4[CH2:25][CH2:26][F:27])=[CH:15][C:14]=3[F:32])[CH2:8]2)[CH2:4][CH2:3]1.CC(O)C>O>[OH2:23].[ClH:1].[CH:2]1([NH:5][CH2:6][C@@H:7]2[C@H:11]([F:12])[CH2:10][N:9]([C:13]3[C:22]([O:23][CH3:24])=[C:21]4[C:16]([C:17](=[O:31])[C:18]([C:28]([OH:30])=[O:29])=[CH:19][N:20]4[CH2:25][CH2:26][F:27])=[CH:15][C:14]=3[F:32])[CH2:8]2)[CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 3776IsopropanolHCID 715287671433857-09-0

Product 1

HCID 71570094HCID 71570094, compoundYield 221.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
72 °C

Procedure

30.0 g (63.0 mmol) of the 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt obtained in Reference Example 1 was added to a solvent mixture of 600 mL of 2-propanol and 90.0 mL of water, and the mixture was heated for dissolution (internal temperature: 72° C.). Then the solution was cooled. After the occurrence of crystallization was observed (internal temperature: 49° C.), the mixture was stirred at around the crystallization temperature (internal temperature: 48 to 49° C.) for 5 minutes. The solution was heated from the crystallization temperate until the internal temperature increased about 10° C. and stirred at this temperature for 30 minutes (internal temperature: 48 to 60° C.). The solution was gradually cooled (cooled by about 1° C. per minute) and stirred at 10° C. or less for 1 hour (internal temperature: 2 to 10° C.). Precipitated crystals were filtrated and washed with a solvent mixture of 143 mL of 2-propanol and 7.5 mL of water to obtain 34.5 g of a white powder of 7-{(3S,4S)-3-[(cyclopropylamino)methyl]-4-fluoropyrrolidine-1-yl}-6-fluoro-1-(2-fluoroethyl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt hydrate (crystals B).

Workup

  1. temperatureThen the solution was cooled
  2. customAfter the occurrence of crystallization
  3. custom(internal temperature: 49° C.)
  4. temperatureThe solution was heated from the crystallization temperate until the internal temperature
  5. temperatureincreased about 10° C.
  6. stirringstirred at this temperature for 30 minutes (internal temperature: 48 to 60° C.)
  7. temperatureThe solution was gradually cooled
  8. temperature(cooled by about 1° C. per minute)
  9. stirringstirred at 10° C. or less for 1 hour (internal temperature: 2 to 10° C.)
  10. customPrecipitated crystals
  11. filtrationwere filtrated
  12. washwashed with a solvent mixture of 143 mL of 2-propanol and 7.5 mL of water

Sources & evidence

ORD record
ord-11ab9a35cddb492796ead1490ad1ab69
Source dataset
uspto-grants-2015_07
Patent number
US09090587B2

Reaction notes

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