26.5 g |
With triethylamine; In toluene; at 0 - 10℃; |
Add 20.4g (0.123mol) of Tropinac (Compound 4), 50mL of toluene to a 250mL three-necked flask, heat to 50 C, add 0.3g (0.003mol) of triethylamine, drop Add 19.0g (0.24mol) of acetyl chloride, and react at 50 C for 3 hours, add 20.5g (0.17mol) of dichlorosulfoxide dropwise, continue the reaction for 5 hours, concentrate in vacuo to a small volume, add 50mL of toluene, and cool to room temperature; A 500mL three-necked flask was charged with 18.2g (0.134mol) of pure N-ethylpyridylamine (Compound 1), 13.7g (0.136mol) of triethylamine, 100mL of toluene, cooled to 0 C, and acetyltropine acid was added dropwise. The solution was reacted overnight at 0-10 C. 80 mL of saturated saline was added and washed five times. The organic phase was added with 27 g (0.23 mol) of 31% hydrochloric acid and heated to 90 C. The reaction was allowed to proceed overnight. The organic phase was separated with ammonia and dilute hydrochloric acid. , Saturated brine, washed with purified water, the organic phase was concentrated in vacuo at 50 C, the concentrated solution was recrystallized with ethyl acetate / n-heptane, the filter cake was washed with n-heptane, and dried in vacuo to obtain 26.5 g of tropinamide, with a purity of 98.8% The yield is 75.9%. |
26.5 g |
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Preparation of Tropicamide (Compound 7): Add 20.4g (0.123mol) to a 250mL three-necked bottleTropic acid (Compound 4), 50mL toluene, heated to 50 , added 0.3g (0.003mol) triethylamine, added dropwise 19.0g (0.24mol) acetyl chloride, reacted at 50 for 3 hours, added dropwise 20.5g (0.17 mol) Dichlorosulfoxide, continue the reaction for 5 hours, concentrate in vacuo to a small volume, add 50 mL of toluene, and cool to room temperature; add 18.2 g (0.134 mol) of pure N-ethylpyridine to another 500 mL three-necked bottle ( Compound 1), 13.7g (0.136mol) of triethylamine, 100mL of toluene, cooled to 0 C, add a solution of acetotropic acid dropwise, react overnight at 0-10 C, add 80mL of saturated brine and wash five times, the organic phase is added 27g (0.23mol) 31% hydrochloric acid, heated to 90 C, reacted overnight, liquid separation, the organic phase was washed with ammonia, dilute hydrochloric acid, saturated brine, purified water, the organic phase was concentrated in vacuo at 50 C, the concentrated solution was with ethyl acetate / N-heptane recrystallized, the filter cake was washed with n-heptane, and dried in vacuum to obtain 26.5 g of tropinamide with a purity of 98.8% and a yield of 75.9%. |