Synthesis and post-processing method of sulpiride or optical isomer thereof

Abstract

The invention relates to a synthesis and post-processing method of sulpiride or an optical isomer thereof, and the synthesis and post-processing method include the following steps: under inert gas protection, heating 2-methoxy-5-aminosulfonyl methyl benzoate or 2-methoxy-5-aminosulfonyl ethyl benzoate and 1-ethyl-2-aminomethyl pyrrolidine or an optical isomer thereof at 80-120 DEG C for a plurality of hours, and after the reaction is completed, adding ethanol for processing, cooling, filtering, washing and drying.

Description

technical field

[0001] The invention relates to the field of medicine, in particular to a synthesis and post-treatment method of sulpiride or an optical isomer thereof. Background technique

[0002] Sulpiride, the chemical name is N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-(sulfamoyl)benzamide; synthesized by the French in 1967 , because it has the effect of treating mental disorders and has few adverse reactions, it has been used clinically for many years at home and abroad.

[0003] Levosulpiride, chemical name (-)-(S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-(sulfamoyl)benzene Formamide. Since it has antiemetic and gastroparesis effects in addition to treating mental disorders, the single isomer compound is more effective and better tolerated than the racemic compound.

[0004] The existing multiple bibliographical reports of the synthetic method of sulpiride or its optical isomers, most of them are without solvent or with ethylene glycol as solvent will 2-me...

Examples

Embodiment 1

[0025] Add 49g of 2-methoxy-5-sulfamoylbenzoic acid methyl ester and (S)-1-ethyl-2-aminomethyltetrahydropyrrolidine 26.5g into the reaction flask, under the protection of nitrogen at 90-100 ℃ for 5 hours, the reaction was completed, cooled to 80 ℃, added 50g of ethanol, stirred and refluxed for 10 minutes, cooled to 5 ℃ and stirred for 2 hours, filtered, washed with ethanol, and dried at 65 ℃. Yield 93.8%, purity 99.2%.

Embodiment 2

[0027] Add 25.9 g of ethyl 2-methoxy-5-sulfamoylbenzoate, 15 g of (S)-1-ethyl-2-aminomethyltetrahydropyrrolidine and 20 g of isopropanol into the reaction flask, 80 ℃ for 36 hours, the reaction is over, add 10 g of ethanol, stir and reflux for 10 minutes, cool to 5 ℃ and stir for 1 hour, filter, wash with ethanol, and dry at 65 ℃. Yield 90.3%, purity 99.1%.

Embodiment 3

[0029] Add 123g of 2-methoxy-5-sulfamoylbenzoic acid methyl ester, 75g of 1-ethyl-2-aminomethyltetrahydropyrrolidine and 100g of ethylene glycol into the reaction flask. React at 100°C for 4-6 hours. When the reaction is over, cool naturally to 80°C, add 190g of ethanol, stir and reflux for 5 minutes, cool to 0°C and stir for 2 hours, filter, wash with ethanol, and dry at 65°C. Yield 85.1%, purity 99.5%.

technical field

[0001] The invention relates to the field of medicine, in particular to a synthesis and post-treatment method of sulpiride or an optical isomer thereof. Background technique

[0002] Sulpiride, the chemical name is N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-(sulfamoyl)benzamide; synthesized by the French in 1967 , because it has the effect of treating mental disorders and has few adverse reactions, it has been used clinically for many years at home and abroad.

[0003] Levosulpiride, chemical name (-)-(S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-(sulfamoyl)benzene Formamide. Since it has antiemetic and gastroparesis effects in addition to treating mental disorders, the single isomer compound is more effective and better tolerated than the racemic compound.

[0004] The existing multiple bibliographical reports of the synthetic method of sulpiride or its optical isomers, most of them are without solvent or with ethylene glycol as solvent will 2-me...

Examples

Embodiment 1

[0025] Add 49g of 2-methoxy-5-sulfamoylbenzoic acid methyl ester and (S)-1-ethyl-2-aminomethyltetrahydropyrrolidine 26.5g into the reaction flask, under the protection of nitrogen at 90-100 ℃ for 5 hours, the reaction was completed, cooled to 80 ℃, added 50g of ethanol, stirred and refluxed for 10 minutes, cooled to 5 ℃ and stirred for 2 hours, filtered, washed with ethanol, and dried at 65 ℃. Yield 93.8%, purity 99.2%.

Embodiment 2

[0027] Add 25.9 g of ethyl 2-methoxy-5-sulfamoylbenzoate, 15 g of (S)-1-ethyl-2-aminomethyltetrahydropyrrolidine and 20 g of isopropanol into the reaction flask, 80 ℃ for 36 hours, the reaction is over, add 10 g of ethanol, stir and reflux for 10 minutes, cool to 5 ℃ and stir for 1 hour, filter, wash with ethanol, and dry at 65 ℃. Yield 90.3%, purity 99.1%.

Embodiment 3

[0029] Add 123g of 2-methoxy-5-sulfamoylbenzoic acid methyl ester, 75g of 1-ethyl-2-aminomethyltetrahydropyrrolidine and 100g of ethylene glycol into the reaction flask. React at 100°C for 4-6 hours. When the reaction is over, cool naturally to 80°C, add 190g of ethanol, stir and reflux for 5 minutes, cool to 0°C and stir for 2 hours, filter, wash with ethanol, and dry at 65°C. Yield 85.1%, purity 99.5%.