8-AZASPIRO[4.5]DECANE synthesis

Yield:-

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 20; for 5 h;Inert atmosphere;Reflux;

Steps:

22.1 step 1 preparation of 8-azaspiro[4.5]dec-8-carbonitrile 11b

lithium aluminiumhydride(0.95 g, 25 mmol) dissolved in 25 mL of anhydrous tetrahydrofuran, cooled to 0 ° C in an ice bath. Argon protection,After the agitation is completely dissolved, 8-Azaspiro[4.5]indole-7,9-dione (836 mg, 5 mmol) was dissolved in 15 mL of anhydrous tetrahydrofuran and slowly added dropwise to lithium aluminiumhydride mixture. After the addition is completed, The reaction solution was transferred to room temperature and stirred for 0.5 hour, and then heated to reflux for 4.5 hours. After TLC monitors the reaction, no raw material remains,When the temperature of the reaction system is lowered to room temperature, Slowly add water (0.95 mL) to the reaction system in turn,15% sodium hydroxide solution (0.95mL),Water (2.85mL),filter,Sodium bicarbonate (1.26 g, 15 mmol) was dissolved in 10 mL of water and mixed with the filtrate.Cool in ice bath to 0 ° C,Cyanogen bromide (656 mg, 6.25 mmol) was dissolved in 5 mL of dichloromethane and slowly added dropwise to the reaction system.The reaction system was stirred at 0 ° C for 0.5 hour and then transferred to room temperature and stirred overnight.The reaction solution was extracted with dichloromethane.Combine the organic layers,The organic layer was washed successively with saturated sodium bicarbonate solution and brine.The organic layer was dried over anhydrous sodium sulfate.Filtered, concentrated under reduced pressure,The intermediate 8-azaspiro[4.5]dec-8-carbonitrile 11b is obtained.Yellow oil 686mg, yield 84%

References:

CN104211708,2018,B Location in patent:Paragraph 0327-0329