Synthesis
General Steps:
Reaction: in a 250 mL round bottom flask, 10 g of ethyl 1-cyclopropyl-6,7-difluoro-8-methoxy-4-yloxy-1,4-dihydroxyquinoline-3-carboxylate (compound of formula 2) and 100 mL of anhydrous methanol were added and stirred until completely dissolved. Subsequently, 13.3 mL of 36% hydrochloric acid was added slowly and dropwise. After addition, the reaction system was heated to 65 °C and the reaction was stirred at this temperature for 15 hours.
Post-treatment: after completion of the reaction, the system was cooled to 10 °C and stirring was continued for 2 hours to promote crystallization. Subsequently, the system was filtered under reduced pressure. The filter cake was washed with 20 mL of anhydrous methanol and subsequently dried under vacuum at 60 °C for 8 h to afford 8.86 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid (compound of formula 3) in 96.83% yield.
References
[1] Patent: CN107778308, 2018, A. Location in patent: Paragraph 0067; 0068; 0069
[2] Asian Journal of Chemistry, 2013, vol. 25, # 11, p. 6079 - 6082
[3] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 5, p. 2558 - 2569
[4] Patent: US4997943, 1991, A
[5] Patent: WO2004/14893, 2004, A2. Location in patent: Page 75; 76
