Preparation method of important intermediate of amisulpride

Abstract

4-amino-5-thiophenol-2-methoxymethyl benzoate is an important intermediate of the antipsychotic drug amisulpride. The invention relates to a preparation method of 4-amino-5-thiophenol-2-methoxymethylbenzoate. The method is mild in reaction conditions, easy to operate and simple in purification process.

Description

technical field

[0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a method for synthesizing methyl 4-amino-5-thiophenol-2-methoxybenzoate. Background technique

[0002] 4-Amino-5-ethanesulfonyl-2-methoxybenzoic acid (Ⅰ) is an important intermediate of the antipsychotic drug amisulpride. Amisulpride is a broad-spectrum antipsychotic drug developed by the French company Sanofi Synthelabo, which is widely used in adult schizophrenia patients with acute and chronic, positive and negative symptoms, in January 1997 Listed in the United States and China in 2001, it has become the first-line drug for the treatment of acute progressive and chronic schizophrenia. The author studied the synthesis of amisulpride intermediate 4-amino-5-thiophenol-2-methoxybenzoic acid methyl ester (Ⅵ), and explored a synthetic method with industrial application prospects.

[0003] In the bibliography report on the synthesis of amisulpride, the key ...

Examples

Embodiment 1

[0020] 0.5 g of methyl 4-amino-2-methoxy-5-thiocyanatobenzoate was dissolved in 6 ml of water and 3 ml of methanol while maintaining the temperature of the solution at 10-15°C and stirring. 0.26g Na 2 S was dissolved in 2 ml of water and added dropwise to the solution. After stirring for 1 h, the reaction temperature was raised to 80°C, and the reaction was continued for 2 h. The reaction mother liquor was filtered, and the pH value of the filtrate was adjusted to 2-3 using 3M hydrochloric acid, and 0.38 g of a yellow solid was obtained by filtration, with a yield of 85%.

Embodiment 2

[0022] 0.5 g of methyl 4-amino-2-methoxy-5-thiocyanatobenzoate was dissolved in 6 ml of water and 3 ml of ethanol, while maintaining the temperature of the solution at 5-10° C. and stirring. 0.26g Na 2 S was dissolved in 2 ml of water and added dropwise to the solution. After stirring for 1 h, the reaction temperature was raised to room temperature, and the reaction was continued for 8 h. The reaction mother liquor was filtered, and the pH value of the filtrate was adjusted to 5-6 with 3M acetic acid, and 0.35 g of a yellow solid was obtained by filtration, with a yield of 78%.

technical field

[0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a method for synthesizing methyl 4-amino-5-thiophenol-2-methoxybenzoate. Background technique

[0002] 4-Amino-5-ethanesulfonyl-2-methoxybenzoic acid (Ⅰ) is an important intermediate of the antipsychotic drug amisulpride. Amisulpride is a broad-spectrum antipsychotic drug developed by the French company Sanofi Synthelabo, which is widely used in adult schizophrenia patients with acute and chronic, positive and negative symptoms, in January 1997 Listed in the United States and China in 2001, it has become the first-line drug for the treatment of acute progressive and chronic schizophrenia. The author studied the synthesis of amisulpride intermediate 4-amino-5-thiophenol-2-methoxybenzoic acid methyl ester (Ⅵ), and explored a synthetic method with industrial application prospects.

[0003] In the bibliography report on the synthesis of amisulpride, the key ...

Examples

Embodiment 1

[0020] 0.5 g of methyl 4-amino-2-methoxy-5-thiocyanatobenzoate was dissolved in 6 ml of water and 3 ml of methanol while maintaining the temperature of the solution at 10-15°C and stirring. 0.26g Na 2 S was dissolved in 2 ml of water and added dropwise to the solution. After stirring for 1 h, the reaction temperature was raised to 80°C, and the reaction was continued for 2 h. The reaction mother liquor was filtered, and the pH value of the filtrate was adjusted to 2-3 using 3M hydrochloric acid, and 0.38 g of a yellow solid was obtained by filtration, with a yield of 85%.

Embodiment 2

[0022] 0.5 g of methyl 4-amino-2-methoxy-5-thiocyanatobenzoate was dissolved in 6 ml of water and 3 ml of ethanol, while maintaining the temperature of the solution at 5-10° C. and stirring. 0.26g Na 2 S was dissolved in 2 ml of water and added dropwise to the solution. After stirring for 1 h, the reaction temperature was raised to room temperature, and the reaction was continued for 8 h. The reaction mother liquor was filtered, and the pH value of the filtrate was adjusted to 5-6 with 3M acetic acid, and 0.35 g of a yellow solid was obtained by filtration, with a yield of 78%.

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