New synthesis process of sultopride hydrochloride

[0046] (1) Preparation of 2-methoxy-5-ethylsulfonylbenzoic acid methyl ester

[0047] In a dry three-necked flask, first drop methanol (385ml), then slowly add concentrated sulfuric acid (38ml) under stirring, control the temperature to be less than 30°C, and finally add 2-methoxy-5-ethanesulfonylbenzoic acid ( 100g); after addition, stir and heat to reflux, react for 4hrs, place it under cooling, suction filter, wash with water until neutral, and obtain white crystal 2-methoxy-5-ethylsulfonylbenzoic acid methyl ester (91.5g), melting point 126.5 -128°C, yield 86.5%.

[0048] (2) preparation of sultopride hydrochloride

[0049] In a 500ml three-necked flask, put ethylene glycol (135ml) first, and then put N-ethyl-2-aminomethyltetrahydropyrrolidine (33.5ml) and 2-methoxy-5-ethanesulfonate successively under stirring. Methyl acylbenzoate (50g); after the injection, heat to 80±5°C and keep it warm for 10hrs. After the reaction, cool to room temperature, then acidify with hydroc...

[0051] (1) Preparation of 2-methoxy-5-ethylsulfonylbenzoic acid methyl ester

[0052] In a dry there-necked flask, first drop methanol (500ml), then slowly add concentrated sulfuric acid (50ml) under stirring, control the temperature below 30°C, and finally add 2-methoxy-5-ethanesulfonylbenzoic acid ( 125g); after addition, stir and heat to reflux, react for 4hrs, cool and place, suction filter, wash with water to neutrality, and obtain white crystal 2-methoxy-5-ethylsulfonylbenzoic acid methyl ester (118.4g), melting point 126.5 -128°C, yield 89.6%.

[0053] (2) preparation of sultopride hydrochloride

[0054] In a 500ml three-necked bottle, put glycerin (55ml) first, then put N-ethyl-2-aminomethyltetrahydropyrrolidine (67ml) and 2-methoxy-5-ethanesulfonylbenzoic acid in turn under stirring Methyl ester (100g); after the injection, heat to 95±5°C and keep it warm for 6hrs. After the reaction, cool to room temperature, then acidify with hydrochloric acid to pH=1 to obtain of...

[0056] (1) Preparation of 2-methoxy-5-ethylsulfonylbenzoic acid methyl ester

[0057]In a dry three-necked flask, first drop methanol (400ml), then slowly add concentrated sulfuric acid (40ml) under stirring, control the temperature below 30°C, and finally add 2-methoxy-5-ethanesulfonylbenzoic acid ( 100g); after adding, stir and heat to reflux, react for 4hrs, place it under cooling, filter with suction, wash with water until neutral, and obtain white crystal 2-methoxy-5-ethylsulfonylbenzoic acid methyl ester (93g), melting point 126.5- 128°C, yield 88%.

[0058] (2) preparation of sultopride hydrochloride

[0059] In a 500ml three-necked flask, put ethylene glycol (135ml) first, and then put N-ethyl-2-aminomethyltetrahydropyrrolidine (33.5ml) and 2-methoxy-5-ethanesulfonate successively under stirring. Methyl acylbenzoate (50g); after the injection, heat to 90±5°C and keep it warm for 7hrs. After the reaction, cool to room temperature, and then acidify with hydrochloric ac...