A method for treating a fluticasone propionate mother liquor
By employing the Hoffmann alkylation reaction and subsequent processing steps, the problem of recovering fluorohalomethanes from the fluticasone propionate mother liquor was solved, enabling the preparation of fluticasone propionate with high purity and high recovery rate, thus reducing environmental pollution.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- HUANGGANG HUMANWELL PHARMACEUTICAL CO LTD
- Filing Date
- 2023-08-22
- Publication Date
- 2026-05-12
AI Technical Summary
In existing technologies, residual fluorohalomethanes in fluticasone propionate mother liquor cannot be effectively recovered, and conventional quenching methods result in violent reactions that affect product purity and recovery rate.
The mixture was subjected to Hoffmann alkylation reaction with amine compounds, followed by extraction, alkali washing, acid washing, concentration, decolorization, filtration, cooling crystallization and drying to quench fluorohalomethanes and recover fluticasone propionate.
The efficient quenching of fluorohalomethanes under mild conditions improves the purity and recovery rate of fluticasone propionate, reduces environmental pollution, and achieves full utilization of the material.
Smart Images
Figure CN117088932B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of mother liquor recycling technology, specifically relating to a method for treating fluticasone propionate mother liquor. Background Technology
[0002] In the synthesis of fluticasone propionate, a large amount of fluorohalomethanes are required. For example, Chinese patent CN 110343143A discloses a method for preparing fluticasone propionate, which includes the following steps: Step 1) Compound 5 is hydrolyzed in the presence of alkali and alcohol solvent to obtain compound 6; Step 2) Compound 6 is reacted with fluorohalomethanes under the condition of reducing salt as catalyst to obtain fluticasone propionate.
[0003]
[0004] The fluorohalomethanes added in step 2) cannot react completely, leaving a large amount of residue in the fluticasone propionate mother liquor. Fluorohalomethanes are toxic and can damage the atmospheric ozone layer, harming the environment. Furthermore, the fluticasone propionate mother liquor also contains fluticasone propionate. Directly discarding the fluticasone propionate mother liquor not only pollutes the environment but also wastes fluticasone propionate.
[0005] Due to the toxicity of fluorohalomethanes to operators and their environmental hazards, fluorohalomethanes need to be quenched before the fluticasone propionate mother liquor can be recycled. However, conventional quenching methods (such as adding a strong alkali and heating for decomposition) involve overly harsh reaction conditions, which can lead to product contamination and affect the recovery rate and purity of fluticasone propionate. Currently, no reasonable method for treating fluticasone propionate mother liquor has been found. Summary of the Invention
[0006] In view of this, the purpose of this invention is to provide a method for treating fluticasone propionate mother liquor. Using the method of this invention to treat fluticasone propionate mother liquor yields fluticasone propionate with high purity and high recovery rate.
[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:
[0008] This invention provides a method for treating fluticasone propionate mother liquor, comprising the following steps:
[0009] Fluticasone propionate mother liquor and amine compounds were mixed and subjected to Hoffmann alkylation reaction to obtain a mixture;
[0010] After removing the first organic solvent from the mixture, it is mixed with the second organic solvent for extraction. The resulting organic phase is then subjected to alkali washing, acid washing, and concentration to obtain a concentrate.
[0011] The concentrate was mixed with a third organic solvent and heated under reflux, followed by decolorization, filtration, cooling and crystallization, and drying to obtain fluticasone propionate.
[0012] Preferably, the amine compound includes diethylamine.
[0013] Preferably, the Hoffmann alkylation reaction is carried out at a temperature of -5 to 30°C for 24 to 72 hours.
[0014] Preferably, the fluticasone propionate mother liquor contains 5-15% fluticasone propionate by mass and 1-10% fluorohalomethanes by mass.
[0015] Preferably, the mass ratio of the amine compound to the fluticasone propionate mother liquor is 1 to 10:50.
[0016] Preferably, the second organic solvent includes one or more of isopropyl acetate, ethyl acetate, and dichloromethane.
[0017] Preferably, the ratio of the second organic solvent to the fluticasone propionate mother liquor is 0.5–2 mL: 1 g.
[0018] Preferably, the alkaline washing reagent includes an aqueous solution of potassium carbonate or an aqueous solution of sodium carbonate.
[0019] Preferably, the acid washing reagent includes an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid.
[0020] Preferably, the reagent used for decolorization is activated carbon, and the ratio of activated carbon to the third organic solvent is 5-15g:1000mL.
[0021] This invention provides a method for treating fluticasone propionate mother liquor, comprising the following steps:
[0022] Fluticasone propionate mother liquor and amine compounds were mixed and subjected to Hoffmann alkylation reaction to obtain a mixture;
[0023] After removing the first organic solvent from the mixture, it is mixed with the second organic solvent for extraction. The resulting organic phase is then subjected to alkali washing, acid washing, and concentration to obtain a concentrate.
[0024] The concentrate was mixed with a third organic solvent and heated under reflux, followed by decolorization, filtration, cooling and crystallization, and drying to obtain fluticasone propionate.
[0025] Compared with the prior art, the present invention has the following beneficial effects:
[0026] The present invention provides a method for treating fluticasone propionate mother liquor. First, the fluticasone propionate mother liquor is mixed with amine compounds and subjected to a Hoffmann alkylation reaction. The Hoffmann alkylation reaction of the amine compounds quenches fluorohalomethanes under mild conditions, reducing the contamination of fluticasone propionate. This solves the problem that conventional quenching methods involve excessively harsh reaction conditions that lead to product contamination. The recovered fluticasone propionate has high purity and a high recovery rate, ensuring full utilization of the material and reducing environmental pollution from fluorohalomethanes and steroidal compounds (fluticasone propionate).
[0027] Data from the examples show that the fluticasone propionate mother liquor treated with the method of the present invention has high purity and high recovery rate, with a purity of ≥99% and a recovery rate of ≥76%. Attached Figure Description
[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0029] Figure 1 The area normalization test results of fluticasone propionate obtained in Example 1 are shown below.
[0030] Figure 2 The area normalization test results of fluticasone propionate obtained in Example 2 are shown below.
[0031] Figure 3 The area normalization test results of fluticasone propionate obtained in Example 3 are shown below.
[0032] Figure 4 The area normalization test results of fluticasone propionate obtained in Comparative Example 1 are shown.
[0033] Figure 5 The area normalization test results of fluticasone propionate obtained in Comparative Example 2 are shown.
[0034] Figure 6 The results of the area normalization test of fluticasone propionate obtained in Comparative Example 3 are shown. Detailed Implementation
[0035] This invention provides a method for treating fluticasone propionate mother liquor, comprising the following steps:
[0036] Fluticasone propionate mother liquor and amine compounds were mixed and subjected to Hoffmann alkylation reaction to obtain a mixture;
[0037] After removing the first organic solvent from the mixture, it is mixed with the second organic solvent for extraction. The resulting organic phase is then subjected to alkali washing, acid washing, and concentration to obtain a concentrate.
[0038] The concentrate was mixed with a third organic solvent and heated under reflux, followed by decolorization, filtration, cooling and crystallization, and drying to obtain fluticasone propionate.
[0039] Unless otherwise specified, all materials and equipment used in this invention are commercially available products in the field.
[0040] In this invention, fluticasone propionate mother liquor and amine compounds are mixed and subjected to Hoffmann alkylation reaction to obtain a mixed solution.
[0041] In this invention, the fluticasone propionate mother liquor preferably includes fluticasone propionate and fluorohalomethanes. The mass content of fluticasone propionate in the fluticasone propionate mother liquor is preferably 5-15%, more preferably 10%, and the mass content of fluorohalomethanes is preferably 1-10%, more preferably 5%.
[0042] In this invention, the fluorohalomethanes preferably include chlorofluoromethane, bromofluoromethane, or iodofluoromethane.
[0043] In this invention, the solvent in the fluticasone propionate mother liquor preferably includes an organic solvent and water, wherein the organic solvent preferably includes methanol or acetone, and the volume ratio of the organic solvent to water is preferably 1 to 10:1; the fluticasone propionate mother liquor preferably also includes alkaline substances and other impurities, wherein the alkaline substances preferably include potassium carbonate, sodium carbonate, or potassium bicarbonate, and the other impurities preferably include compounds 1 to 4, wherein the structural formulas of compounds 1 to 4 are shown in formulas 1 to 4 respectively, wherein compound 1 is fluticasone propionate intermediate E, and its mass content in the fluticasone propionate mother liquor is preferably 2 to 4%; compound 2 is a mercaptooxide, and its mass content in the fluticasone propionate mother liquor is preferably 1 to 2%; compound 3 is a disulfide, and its mass content in the fluticasone propionate mother liquor is preferably 0.5 to 2%; and compound 4 is a haloalkylation impurity, and its mass content in the fluticasone propionate mother liquor is preferably 0.5 to 2%.
[0044]
[0045] In this invention, the fluticasone propionate mother liquor is preferably the mother liquor obtained after preparing fluticasone propionate according to Chinese Patent CN 110343143A.
[0046] In this invention, the amine compound preferably includes diethylamine, and the product of the reaction of the amine compound is easily removed.
[0047] In this invention, the mass ratio of the amine compound to the fluticasone propionate mother liquor is preferably 1 to 10:50, more preferably 8 to 10:50.
[0048] In this invention, the reaction temperature of the Hoffmann alkylation reaction is preferably -5 to 30°C, more preferably 5 to 25°C; the reaction time is preferably 24 to 72 h, more preferably 48 h; the Hoffmann alkylation reaction refers to the reaction of fluorohalomethanes in the fluticasone propionate mother liquor with amine compounds. The Hoffmann alkylation reaction can quench fluorohalomethanes. If the reaction temperature is too high, various side reactions will occur, resulting in more impurities, which will affect the yield and purity of fluticasone propionate.
[0049] In this invention, the Hoffmann alkylation reaction is preferably carried out under stirring conditions, and the stirring speed is preferably 100-400 r / min.
[0050] In this invention, the residual concentration of fluorohalomethanes in the mixture is preferably less than 100 mg / L.
[0051] After obtaining the mixture, the present invention removes the first organic solvent from the mixture and mixes it with the second organic solvent for extraction. The obtained organic phase is then subjected to alkali washing, acid washing and concentration in sequence to obtain a concentrate.
[0052] In this invention, the method for removing the first organic solvent from the mixture is preferably vacuum concentration, and the vacuum concentration temperature is preferably 40-50°C, more preferably 45°C; the pressure is preferably -0.09 to -0.1 kPa. After vacuum concentration, the first organic solvent and unreacted amine compounds in the mixture are removed, and the first organic solvent is the organic solvent in the fluticasone propionate mother liquor.
[0053] In this invention, the second organic solvent preferably includes one or more of isopropyl acetate, ethyl acetate and dichloromethane, more preferably isopropyl acetate. Using isopropyl acetate for the extraction is more environmentally friendly and stable. During the extraction process, fluticasone propionate is extracted into the second organic solvent.
[0054] In this invention, the preferred ratio of the second organic solvent to the fluticasone propionate mother liquor is 0.5-2 mL:1 g, more preferably 1 mL:1 g.
[0055] In this invention, the mixed solution obtained by extraction is preferably allowed to stand and separate into an aqueous phase and an organic phase. The standing and separation time is preferably 0.5 h, and the temperature is preferably room temperature.
[0056] In this invention, the alkaline washing reagent preferably includes an aqueous solution of potassium carbonate or an aqueous solution of sodium carbonate, more preferably an aqueous solution of potassium carbonate, and the mass concentration of both the aqueous solution of potassium carbonate and the aqueous solution of sodium carbonate is preferably 10%; the volume ratio of the alkaline washing reagent to the second organic solvent is preferably 0.5 to 5.0:1, more preferably 1:1.
[0057] In this invention, the alkaline washing is preferably performed 1 to 3 times, more preferably 2 times. The alkaline washing is to remove unreacted raw materials, including fluticasone propionate intermediate E (compound 1), also known as (6A,11B,16A,17A)-6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)-androst-1,4-diene-17-thiocarboxylic acid.
[0058] In this invention, the pickling reagent preferably includes an aqueous solution of hydrochloric acid or an aqueous solution of sulfuric acid, more preferably an aqueous solution of hydrochloric acid, and the concentration of both the aqueous solution of hydrochloric acid and the aqueous solution of sulfuric acid is preferably 1 mol / L; the volume ratio of the pickling reagent to the second organic solvent is preferably 0.5 to 5.0:1, more preferably 1:1.
[0059] In this invention, the acid washing is preferably performed 1 to 3 times, more preferably 2 times, and the acid washing is to remove the reaction products of fluorohalomethanes and amine compounds in the fluticasone propionate mother liquor.
[0060] In this invention, the concentration is preferably carried out in a concentration vessel under reduced pressure. The temperature of the reduced pressure concentration is preferably 40-50°C, more preferably 45°C; the pressure is preferably -0.09 to -0.1 kPa; and the degree of concentration is preferably to concentrate the organic solvent in the organic phase to dryness.
[0061] After obtaining the concentrate, the present invention mixes the concentrate with a third organic solvent, heats and refluxes it, and then performs decolorization, filtration, cooling and crystallization and drying in sequence to obtain fluticasone propionate.
[0062] In this invention, the third organic solvent preferably includes one or more of alcohol solvents, acetone and tetrahydrofuran, wherein the alcohol solvent preferably includes ethanol or isopropanol, more preferably isopropanol.
[0063] In this invention, the volume ratio of the third organic solvent to the second organic solvent is preferably 1:1.
[0064] In this invention, the preferred temperature for the heating and reflux is 80-85°C, and a clear solution is obtained after the heating and reflux.
[0065] In this invention, the reagent used for decolorization is preferably activated carbon, and the ratio of activated carbon to the third organic solvent is preferably 5-15g:1000mL, more preferably 10g:1000mL. In this invention, it is preferable to add activated carbon to the clear solution obtained after heating and reflux and continue refluxing, and the reflux time is preferably 1h.
[0066] The present invention does not have any special requirements for the filtration method. After filtration, a filtrate and a filter cake are obtained. The filter cake is preferably washed with a third organic solvent. The resulting wash liquid and filtrate are combined and then cooled to crystallize. The temperature of the third organic solvent in the washing is preferably -5 to 0°C.
[0067] In this invention, the cooling rate for the cooling crystallization is preferably 10-20℃ / h, the final temperature for the cooling crystallization is preferably -5 to 0℃, and after reaching the final temperature for the cooling crystallization, it is preferable to continue to keep warm for 2h.
[0068] In this invention, the cooling and crystallization process preferably includes filtration to obtain filtrate and filter cake. The filter cake is then washed with a third organic solvent and dried. The temperature of the third organic solvent during the washing process is preferably -5 to 0°C.
[0069] In this invention, the drying temperature is preferably 50-60°C, more preferably 55°C, and the drying time is preferably 24 hours. Fluticasone propionate is obtained after drying, and the purity of the fluticasone propionate is preferably ≥99%.
[0070] To further illustrate the present invention, the method for processing fluticasone propionate mother liquor of the present invention will be described in detail below with reference to the accompanying drawings and embodiments, but these should not be construed as limiting the scope of protection of the present invention.
[0071] Example 1
[0072] 1) Quenching: Take 50g of fluticasone propionate mother liquor (containing 5g of fluticasone propionate and 2g of fluorobromomethane), add 8g of diethylamine, control the reaction temperature at 25℃ and react for 48h, and take a sample to detect 54ppm of fluorobromomethane residue.
[0073] 2) Extraction: Concentrate the organic solvent in the quenched mother liquor to dryness under reduced pressure. Add 50 mL of isopropyl acetate and stir to dissolve. After the solution is clear, let it stand for 0.5 h. Separate layers are formed. Discard the aqueous phase. Wash the organic phase with 50 mL of 10 wt% potassium carbonate solution, and then wash twice with 50 mL of 1M hydrochloric acid. Finally, transfer the organic phase to a concentration vessel and concentrate to dryness under reduced pressure.
[0074] 3) Refining: Add 100 mL of isopropanol to the concentrate obtained in step 2), heat to 80°C, reflux to dissolve, then add 1 g of activated carbon, reflux for decolorization for 1 h, filter, wash the filter cake with 5 mL of isopropanol, and combine the filtrates. Slowly cool the filtrate to 0°C and keep it at this temperature for crystallization for 2 h, filter, wash the filter cake with 5 mL of 0°C isopropanol, and dry to obtain 3.8 g of fluticasone propionate with a purity of 99.15%. The area normalization test results are as follows. Figure 1 As shown.
[0075] Example 2
[0076] 1) Quenching: Take 50g of fluticasone propionate mother liquor (containing 5g of fluticasone propionate and 2g of fluorobromomethane), add 10g of diethylamine, control the reaction temperature at 15℃ and react for 24h, and take a sample to detect 78ppm of fluorobromomethane residue.
[0077] 2) Extraction: Concentrate the organic solvent in the quenched mother liquor to dryness under reduced pressure. Add 50 mL of isopropyl acetate and stir to dissolve. After the solution is clear, let it stand for 0.5 h. Separate layers are formed. Discard the aqueous phase. Wash the organic phase with 50 mL of 10 wt% potassium carbonate solution, and then wash twice with 50 mL of 1M hydrochloric acid. Finally, transfer the organic phase to a concentration vessel and concentrate to dryness under reduced pressure.
[0078] 3) Refining: Add 100 mL of isopropanol to the concentrate obtained in step 2), heat to 80 °C, reflux to dissolve, then add 1 g of activated carbon, reflux for decolorization for 1 h, filter, wash the filter cake with 5 mL of isopropanol, and combine the filtrates. Slowly cool the filtrate to 0 °C and keep it at this temperature for crystallization for 2 h, filter, wash the filter cake with 5 mL of 0 °C isopropanol, and dry to obtain 4.0 g of fluticasone propionate with a purity of 99.12%. The area normalization test results are as follows. Figure 2 As shown.
[0079] Example 3
[0080] 1) Quenching: Take 50g of fluticasone propionate mother liquor (containing 5g of fluticasone propionate and 2g of fluorobromomethane), add 10g of diethylamine, control the reaction temperature at 5℃ and react for 72h, and take a sample to detect 74ppm of fluorobromomethane residue.
[0081] 2) Extraction: Concentrate the organic solvent in the quenched mother liquor to dryness under reduced pressure. Add 50 mL of isopropyl acetate and stir to dissolve. After the solution is clear, let it stand for 0.5 h. Separate layers are formed. Discard the aqueous phase. Wash the organic phase with 50 mL of 10 wt% potassium carbonate solution, and then wash twice with 50 mL of 1M hydrochloric acid. Finally, transfer the organic phase to a concentration vessel and concentrate to dryness under reduced pressure.
[0082] 3) Refining: Add 100 mL of isopropanol to the concentrate obtained in step 2), heat to 80 °C, reflux to dissolve, then add 1 g of activated carbon, reflux for decolorization for 1 h, filter, wash the filter cake with 5 mL of isopropanol, and combine the filtrates. Slowly cool the filtrate to 0 °C and keep it at this temperature for crystallization for 2 h, filter, wash the filter cake with 5 mL of 0 °C isopropanol, and dry to obtain 4.1 g of fluticasone propionate with a purity of 99.25%. The area normalization test results are as follows. Figure 3 As shown.
[0083] Comparative Example 1
[0084] 1) Quenching: Take 50g of fluticasone propionate mother liquor (containing 5g of fluticasone propionate and 2g of fluorobromomethane), add 10g of diethylamine, control the reaction temperature at 45℃ and react for 24h, and take a sample to detect fluorobromomethane residue of 36ppm.
[0085] 2) Extraction: Concentrate the organic solvent in the quenched mother liquor to dryness under reduced pressure. Add 50 mL of isopropyl acetate and stir to dissolve. After the solution is clear, let it stand for 0.5 h. Separate layers are formed. Discard the aqueous phase. Wash the organic phase with 50 mL of 10 wt% potassium carbonate solution, and then wash twice with 50 mL of 1M hydrochloric acid. Finally, transfer the organic phase to a concentration vessel and concentrate to dryness under reduced pressure.
[0086] 3) Refining: Add 100 mL of isopropanol to the concentrate obtained in step 2), heat to 80 °C, reflux to dissolve, then add 1 g of activated carbon, reflux for decolorization for 1 h, filter, wash the filter cake with 5 mL of isopropanol, and combine the filtrates. Slowly cool the filtrate to 0 °C and keep it at this temperature for crystallization for 2 h, filter, wash the filter cake with 5 mL of 0 °C isopropanol, and dry to obtain 3.5 g of fluticasone propionate with a purity of 98.63%. The area normalization test results are as follows: Figure 4 As shown.
[0087] Comparative Example 2
[0088] 1) Extraction: Take 50g of fluticasone propionate mother liquor (containing 5g fluticasone propionate and 2g fluorobromomethane), and test for fluorobromomethane residue of 40,000ppm. Concentrate the organic solvent in the mother liquor to dryness under reduced pressure, add 50mL of isopropyl acetate and stir to dissolve. After dissolving completely, let stand for 0.5h. Separate layers, discard the aqueous phase, wash the organic phase with 50mL of 10wt% potassium carbonate solution, and then wash twice with 50mL of 1M hydrochloric acid. Finally, transfer the organic phase to a concentration vessel and concentrate to dryness under reduced pressure.
[0089] 2) Refining: Add 100 mL of isopropanol to the concentrate obtained in step 1), heat to 80 °C, reflux to dissolve, then add 1 g of activated carbon, reflux for decolorization for 1 h, filter, wash the filter cake with 5 mL of isopropanol, and combine the filtrates. Slowly cool the filtrate to 0 °C and keep it at this temperature for crystallization for 2 h, filter, wash the filter cake with 5 mL of 0 °C isopropanol, and dry to obtain 3.5 g of fluticasone propionate with a purity of 99.19%. The area normalization test results are as follows: Figure 5 As shown.
[0090] Comparative Example 3
[0091] 1) Quenching: Take 50g of fluticasone propionate mother liquor (containing 5g of fluticasone propionate and 2g of fluorobromomethane), add 10g of sodium hydroxide, control the reaction temperature at 25℃ and react for 48h, and take a sample to detect 87ppm of fluorobromomethane residue.
[0092] 2) Extraction: Concentrate the organic solvent in the quenched mother liquor to dryness under reduced pressure. Add 50 mL of isopropyl acetate and stir to dissolve. After the solution is clear, let it stand for 0.5 h. Separate layers are formed. Discard the aqueous phase. Wash the organic phase with 50 mL of 10 wt% potassium carbonate solution, and then wash twice with 50 mL of 1M hydrochloric acid. Finally, transfer the organic phase to a concentration vessel and concentrate to dryness under reduced pressure.
[0093] 3) Refining: Add 100 mL of isopropanol to the concentrate obtained in step 2), heat to 80 °C, reflux to dissolve, then add 1 g of activated carbon, reflux for decolorization for 1 h, filter, wash the filter cake with 5 mL of isopropanol, and combine the filtrates. Slowly cool the filtrate to 0 °C and keep it at this temperature for crystallization for 2 h, filter, wash the filter cake with 5 mL of 0 °C isopropanol, and dry to obtain 3.5 g of fluticasone propionate with a purity of 94.15%. The area normalization test results are as follows: Figure 6 As shown.
[0094] In Examples 1-3 of this invention, the yield of fluticasone propionate was 76-82%, while in Comparative Examples 1-3, the yield of fluticasone propionate was only 70%. It can be seen that the method for treating the fluticasone propionate mother liquor provided by this invention reduces the impurities of fluticasone propionate and improves the yield of fluticasone propionate.
[0095] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, not all embodiments. People can obtain other embodiments based on the present invention without creative effort, and these embodiments all fall within the protection scope of the present invention.
Claims
1. A method for treating fluticasone propionate mother liquor, characterized in that, Includes the following steps: Fluticasone propionate mother liquor and amine compounds were mixed and subjected to Hoffmann alkylation reaction to obtain a mixture; After removing the first organic solvent from the mixture, it is mixed with the second organic solvent for extraction. The resulting organic phase is then subjected to alkali washing, acid washing, and concentration to obtain a concentrate. The concentrate was mixed with a third organic solvent and heated under reflux, followed by decolorization, filtration, cooling crystallization and drying to obtain fluticasone propionate. The amine compound is diethylamine; the Hoffmann alkylation reaction is carried out at a temperature of -5 to 30°C for 24 to 72 hours.
2. The processing method according to claim 1, characterized in that, The fluticasone propionate mother liquor contains 5-15% fluticasone propionate and 1-10% fluorohalomethanes.
3. The processing method according to claim 2, characterized in that, The mass ratio of the amine compound to the fluticasone propionate mother liquor is 1 to 10:
50.
4. The processing method according to claim 1, characterized in that, The second organic solvent includes one or more of isopropyl acetate, ethyl acetate, and dichloromethane.
5. The processing method according to claim 1 or 4, characterized in that, The ratio of the second organic solvent to the fluticasone propionate mother liquor is 0.5–2 mL: 1 g.
6. The processing method according to claim 1, characterized in that, The alkaline washing reagent includes an aqueous solution of potassium carbonate or an aqueous solution of sodium carbonate.
7. The processing method according to claim 1, characterized in that, The pickling reagents include aqueous solutions of hydrochloric acid or sulfuric acid.
8. The processing method according to claim 1, characterized in that, The reagent used for decolorization is activated carbon, and the ratio of activated carbon to the third organic solvent is 5-15g:1000mL.