反应详情

温度

72 °C

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).

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