93793-83-0

108-24-7

78273-80-0

93793-83-0

1. 58 g (0.930 mol, 90% purity) of potassium hydroxide was dissolved in 1160 g of water and cooled to 20-25 °C. Subsequently 300 g (0.854 mol) of roxartan oxalate (compound 9, prepared in Example 7) was added and mixed with stirring. 2. Ethyl acetate (600 g + 450 g) was added to the reaction system, the organic phases were separated, combined, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 251 g of Roxaidine (compound 8). 3. 251g of Roxaidine was dissolved in 500g of glacial acetic acid and 170g of acetic anhydride was added. Heat and reflux for 2 h. After confirming that the reaction is complete, concentrate under reduced pressure to remove the acetic acid and cool to 15-20 °C. 4. 600 g of water was added followed by 600 g of ethyl acetate. The pH was adjusted to 9-10 with an aqueous solution containing 300 g of potassium carbonate under stirring. extracted with ethyl acetate (400 g + 300 g), the organic phases were combined, dried with anhydrous sodium sulfate, and the filtrate was concentrated by filtration to give 280 g of ropibutyl acetate (Compound 10). 5. 280 g (0.804 mol) of ropivo butyl acetate was dissolved in 1400 g of acetone and cooled to 0-5 °C. The solution was added dropwise to a mixture containing 32 g of hydrogen chloride. A solution of ethyl acetate containing 32 g of hydrogen chloride was added dropwise and a solid was precipitated. Crystallized at 0-5 °C for 35 h, filtered and dried to give 295 g of rozatidine acetate hydrochloride (theoretical yield: 328.58 g, calculated based on 300 g of compound 9; yield: 89.8%).