- Practical and scalable synthesis of beclomethasone dipropionate
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Beclomethasone dipropionate (1) is a synthetic corticosteroid with anti-inflammatory, antipruritic, and anti-allergy properties. It is widely used to treat asthma, allergic rhinitis, and dermatoses. However, existing synthetic routes to this active pharmaceutical ingredient (API) contain steps resulting in low and/or inconsistent yields, and use obsolete reagents. Such inconsistencies coupled with a lack of reliable experimental data makes laboratory-scale and large-scale synthesis of this API difficult and time-consuming. In this paper, we report a practical and scalable approach to synthesize 1 from the readily available steroidal intermediate, 16β-methyl epoxide (3, DB-11). A gram-scale to kilogram-scale synthesis of 1 was achieved with 82% yield, using a cost-effective and scalable methodology. Selective propionylation of the hydroxyl groups at C17 and C21 demonstrate the fact that this approach can be conveniently implemented in fine chemical industries.
- Welideniya, Dhanushi T.,Jayathilaka, Adeesha S.,Acharige, Anjana Delpe,Samanthi,Wanninayake, Umayangani K.,Perera, Shashika S.,Rajapaksha, Weranga,Fernando, Chamod C.,Hewadikaram, Madhavi,Buddhika, Janani,Gunasekara, Pivini,Karunaratne, Veranja,Amaratunga,Gunasekera, Dinara S.
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- Beclomethasone dipropionate intermediate and preparation method thereof
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The invention provides a beclomethasone dipropionate intermediate and a preparation method thereof. The preparation method of beclomethasone dipropionate comprises the following steps: A) in a first organic solvent, reacting a compound DB11, ortho-propionate and p-toluenesulfonic acid to obtain an intermediate shown as a formula I; B) dropwise adding an aluminum trichloride solution into the intermediate shown in the formula I, reacting, adding a second organic solvent after reaction, and separating an organic layer to obtain an intermediate shown in a formula II; C) adding a catalyst and a propionylation reagent into the intermediate shown in the formula II and reacting to obtain an intermediate shown in a formula III; D) dropwise adding hydrochloric acid into the intermediate shown in the formula III, reacting, and separating an organic layer after reaction to obtain a beclomethasone dipropionate crude product. The reaction route is shown in the description. The preparation method disclosed by the invention is environment-friendly, low in energy consumption and high in product purity and yield.
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Paragraph 0043; 0050; 0052; 0055; 0062; 0064; 0067; 0074
(2020/11/25)
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- A dipropionate double-c ester synthesis method free of organic solvents
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The invention relates to a synthetic method of a beclomethasone dipropionate organic-free solvent. According to the method, beclomethasone 11, 17, 21-tripropionate is taken as the raw material and reacts in an organic solvent with a gluconic acid solution or an aqueous solution of ester capable of being converted into gluconic acid in water to prepare the beclomethasone dipropionate organic-free solvent.
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Paragraph 0041; 0042; 0044; 0045; 0046; 0048-0050; 0053
(2018/09/26)
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- A dipropionate double-c ester synthesis method (by machine translation)
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The invention relates to a dipropionate 11, 17, 21 - three-c ester as the raw material, in the organic solvent with the gluconic acid water solution or can be in the water is converted into the ester of gluconic acid aqueous solution reaction preparation dipropionate double-c ester synthesis method. (by machine translation)
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Paragraph 0043-0066
(2018/02/22)
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- Aerosol formulations containing P134a and particulate medicaments
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This invention relates to a pharmaceutical aerosol formulation containing a particulate medicament which is salmeterol or a physiologically acceptable salt or solvate thereof end 1,1,1,2-tetrafluoroethane as propellant, which formulation is free of surfactant or has less than 0.0001 % w/w surfactant based on the weight of medicament. The formulation may contain a further particulate medicament which is salbutamol, beclomethasone dipropionate or a physiologically acceptable salt or solvate thereof. A method of treating respiratory disorders which comprises administration by inhalation of an effective amount of the pharmaceutical aerosol formulation is also described.
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- Novel 9α-fluoro- or chloro-corticosteroid esters and a process for their preparation
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Novel esters of 9α-fluoro- and chloro-corticosteroids of the formula STR1 wherein Y is chlorine or OR1, R1 and R2 represent an acyl group of 2-6 carbon atoms or a benzoyl group and where R1 and R2 can be the same or different in the same molecule, R3 is methyl or fluorine in either the α- or β- orientation, X is chlorine or fluorine, and the C1 C2 bond can be saturated or not, especially those compounds of the formula STR2 wherein Y and R2 have the significance given above, are prepared by reacting the respective 9β,11β-epoxy compounds with hydrogen fluoride or chloride.
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