Hydrochloric Acid → 364069-13-6

Participants

Reaction Conditions

Reaction Steps

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%).

Provenance & Evidence