Preparation method of medical intermediate

[0021] Add 153g of toluene to a 1L reaction flask, add 25g of intermediate 1 under stirring, and then add 11.78g of tetrabutylammonium bisulfate and about 40% potassium hydroxide aqueous solution. The temperature of the system was lowered to 5-10°C, and 12 g of tert-butyl bromoacetate was added dropwise at 7°C. Control the temperature at 5-10°C, stir for 45 minutes, then raise the system to room temperature, control the temperature at 23-25°C and stir for 1 hour. TLC monitoring (n-hexane: ethyl acetate = 2:1), the reaction of raw materials was complete. Add 150g of water, then add 160g of ethyl acetate for extraction and phase separation, collect the organic phase and wash with 152g of water for phase separation. After concentrating, 32 g of reddish-brown oil was obtained. Add 28ml of benzyl alcohol and 8ml of n-propanol to the oil, stir to dissolve, then add 160ml of n-heptane, the system is cloudy, heat to reflux to dissolve, then stir and cool down to 10-20°C, keep warm a...

[0023] Add 153g of toluene to the 1L reaction flask, add 25g of intermediate 1 under stirring, then add 11.78g of tetrabutylammonium bisulfate and about 40% potassium hydroxide aqueous solution (116g of potassium hydroxide is added to 174g of drinking water, stir to dissolve ). The temperature of the system was lowered to 5-10°C, and 12 g of tert-butyl bromoacetate was added dropwise at 7°C. Control the temperature at 5-10°C, stir for 45 minutes, then raise the system to room temperature, control the temperature at 23-25°C and stir for 1 hour. TLC monitoring (n-hexane: ethyl acetate = 2:1), the reaction of raw materials was complete. Add 150g of water, then add 160g of ethyl acetate for extraction and phase separation, collect the organic phase and wash with 152g of water for phase separation. After concentrating, 32 g of oily substance was obtained. Add 48ml of n-propanol to the oil, stir to dissolve, then add 240ml of n-hexane, the system becomes cloudy, heat to reflux to...

[0025] Add 153g of toluene to a 1L reaction flask, add 25g of intermediate 1 under stirring, and then add 11.78g of tetrabutylammonium bisulfate and about 40% potassium hydroxide aqueous solution. The temperature of the system was lowered to 5-10°C, and 12 g of tert-butyl bromoacetate was added dropwise at 7°C. Control the temperature at 5-10°C, stir for 45 minutes, then raise the system to room temperature, control the temperature at 23-25°C and stir for 1 hour. TLC monitoring (n-hexane: ethyl acetate = 2:1), the reaction of raw materials was complete. Add 150g of water, then add 160g of ethyl acetate for extraction and phase separation, collect the organic phase and wash with 152g of water for phase separation. After concentrating, 32 g of oily substance was obtained. Add 48ml of n-butanol to the oil, stir to dissolve, then add 240ml of n-hexane, the system becomes cloudy, heat to reflux to dissolve, then stir and cool down to 10-20°C, keep warm and crystallize for 1-2 hou...