CN-117088932-B - Method for treating fluticasone propionate mother liquor

Abstract

The invention belongs to the technical field of mother liquor recycling, and particularly relates to a method for treating fluticasone propionate mother liquor. According to the method for treating the fluticasone propionate mother liquor, the fluticasone propionate mother liquor and the amine compound are mixed for carrying out the Huffman alkylation reaction, fluorohalomethane is quenched under the mild condition by utilizing the Huffman alkylation reaction of the amine compound, the impurity of the fluticasone propionate is reduced, the purity of the recovered fluticasone propionate is high, the recovery rate of the fluticasone propionate product is high, materials are fully utilized, and the pollution of fluorohalomethane and steroid compounds (fluticasone propionate) to the environment is reduced.

Inventors

• ZHANG CHONG
• MA LULU
• WANG RUIKANG
• ZUO QUAN
• CAI XIAO
• WU QIUFENG
• NI WENFEI
• WANG YANG
• ZHAO JING
• YING JUAN
• LIU LIN

Assignees

• 黄冈人福药业有限责任公司

Dates

Publication Date

20260512

Application Date

20230822

Claims (8)

1. 1. The method for treating the fluticasone propionate mother liquor is characterized by comprising the following steps of: Mixing the fluticasone propionate mother liquor with an amine compound to perform a Huffman alkylation reaction to obtain a mixed liquor; removing the first organic solvent in the mixed solution, mixing the mixed solution with the second organic solvent for extraction, and sequentially performing alkali washing, acid washing and concentration on the obtained organic phase to obtain a concentrate; mixing the concentrate with a third organic solvent, heating and refluxing, and then sequentially decoloring, filtering, cooling, crystallizing and drying to obtain fluticasone propionate; the amine compound is diethylamine, the reaction temperature of the Huffman alkylation reaction is-5-30 ℃, and the reaction time is 24-72 h.
2. 2. The treatment method according to claim 1, wherein the mass content of fluticasone propionate in the fluticasone propionate mother liquor is 5-15% and the mass content of fluorohalogenomethane is 1-10%.
3. 3. The treatment method according to claim 2, wherein the mass ratio of the amine compound to the fluticasone propionate mother liquor is 1-10:50.
4. 4. The process of claim 1, wherein the second organic solvent comprises one or more of isopropyl acetate, ethyl acetate, and methylene chloride.
5. 5. The method according to claim 1 or 4, wherein the dosage ratio of the second organic solvent to the fluticasone propionate mother liquor is 0.5-2 ml/1 g.
6. 6. The process of claim 1, wherein the alkaline wash reagent comprises an aqueous potassium carbonate solution or an aqueous sodium carbonate solution.
7. 7. The process of claim 1, wherein the pickling reagent comprises aqueous hydrochloric acid or aqueous sulfuric acid.
8. 8. The method according to claim 1, wherein the reagent used for decoloring is activated carbon, and the ratio of the activated carbon to the third organic solvent is 5-15 g/1000 ml.

Description

Method for treating fluticasone propionate mother liquor Technical Field The invention belongs to the technical field of mother liquor recycling, and particularly relates to a method for treating fluticasone propionate mother liquor. Background In the synthesis process of fluticasone propionate, a large amount of fluorohalomethane is needed, for example, chinese patent CN 110343143A discloses a preparation method of fluticasone propionate, which comprises the following steps that 1) a compound 5 is hydrolyzed in the presence of alkali and an alcohol solvent to obtain a compound 6, and 2) the compound 6 is reacted with fluorohalomethane under the condition that a reducing salt is used as a catalyst to obtain the fluticasone propionate. The fluorohalogenomethane added in the step 2) cannot completely react, a large amount of fluorohalogenomethane remains in the fluticasone propionate mother liquor, the fluorohalogenomethane has toxicity, and the atmospheric ozone layer can be damaged, so that the environment is endangered. Meanwhile, the fluticasone propionate mother liquor also contains fluticasone propionate, and the fluticasone propionate mother liquor is directly discarded, so that the environment is polluted, and the fluticasone propionate is wasted. Because of toxicity of fluorohalomethane to operators and harm to the environment, fluorohalomethane needs to be quenched and then recycled to the mother liquor of fluticasone propionate, and the conventional quenching method (such as adding strong alkali for heating and decomposing) has too severe reaction conditions, which can cause impurity of products and affect the recovery rate and purity of the fluticasone propionate. At present, a reasonable method for treating fluticasone propionate mother liquor is not found. Disclosure of Invention In view of the above, the present invention aims to provide a method for treating fluticasone propionate mother liquor. The method for treating the fluticasone propionate mother liquor has the advantages that the purity of the obtained fluticasone propionate is high, and the recovery rate is high. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides a method for treating fluticasone propionate mother liquor, which comprises the following steps: Mixing the fluticasone propionate mother liquor with an amine compound to perform a Huffman alkylation reaction to obtain a mixed liquor; removing the first organic solvent in the mixed solution, mixing the mixed solution with the second organic solvent for extraction, and sequentially performing alkali washing, acid washing and concentration on the obtained organic phase to obtain a concentrate; And mixing the concentrate with a third organic solvent, heating and refluxing, and then sequentially decoloring, filtering, cooling, crystallizing and drying to obtain the fluticasone propionate. Preferably, the amine compound comprises diethylamine. Preferably, the reaction temperature of the Huffman alkylation reaction is-5-30 ℃ and the reaction time is 24-72 h. Preferably, the mass content of the fluticasone propionate in the fluticasone propionate mother liquor is 5-15%, and the mass content of the fluorohalogenomethane is 1-10%. Preferably, the mass ratio of the amine compound to the fluticasone propionate mother liquor is 1-10:50. Preferably, the second organic solvent includes one or more of isopropyl acetate, ethyl acetate and methylene chloride. Preferably, the dosage ratio of the second organic solvent to the fluticasone propionate mother liquor is 0.5-2 mL/1 g. Preferably, the alkaline cleaning agent comprises an aqueous potassium carbonate solution or an aqueous sodium carbonate solution. Preferably, the agent for pickling comprises aqueous hydrochloric acid or aqueous sulfuric acid. Preferably, the reagent used for decoloring is activated carbon, and the dosage ratio of the activated carbon to the third organic solvent is 5-15 g/1000 mL. The invention provides a method for treating fluticasone propionate mother liquor, which comprises the following steps: Mixing the fluticasone propionate mother liquor with an amine compound to perform a Huffman alkylation reaction to obtain a mixed liquor; removing the first organic solvent in the mixed solution, mixing the mixed solution with the second organic solvent for extraction, and sequentially performing alkali washing, acid washing and concentration on the obtained organic phase to obtain a concentrate; And mixing the concentrate with a third organic solvent, heating and refluxing, and then sequentially decoloring, filtering, cooling, crystallizing and drying to obtain the fluticasone propionate. Compared with the prior art, the invention has the following beneficial effects: According to the method for treating the fluticasone propionate mother liquor, the fluticasone propionate mother liquor and the amine compound are mixed for carrying out the Huffman al