- Preparation method of betamethasone epoxide
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The invention provides a preparation method of a betamethasone epoxide, which comprises the steps of step 1, preparing a first reaction solution containing a compound II by using a compound I based onan esterification reaction; step 2, based on a bromine hydroxylation reaction, preparing a second reaction solution containing a compound III by using the first reaction solution; and 3, based on a hydrolysis reaction, preparing a betamethasone epoxide IV crude product by using the second reaction solution. The betamethasone epoxide IV is synthesized from the compound I by adopting a one-pot method, the method has the advantages of high yield, simplicity and safety in operation, low cost, small pollution and the like, and the method is stable and easy to realize industrial production.
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Paragraph 0098; 0101-0114; 0115; 0118-0121; 0122; 0125-0128
(2020/12/15)
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- A novel route for the preparation of betamethasone from 9α-hydroxyandrost-4-ene-3,17-dione (9αOH-AD) by chemical synthesis and fermentation
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A novel and efficient synthesis of betamethasone has been developed from the readily available 9α-hydroxyandrost-4-ene-3,17-dione (9αOH-AD). The 16α-methyl was introduced stereoselectively with CH3Br and converted to the 16β-methyl, the 17-side chain was installed with 2-chlorovinyl ethyl ether in the place of the toxic KCN/HOAc, and a mild fermentation was employed for the 1,2-dehydrogenation, replacing the DDQ oxidation. By adjustments and improvements of the steps, this route produced betamethasone in 11 steps with a 22.9% overall yield, showing its potential for industrial application with relatively low toxicity and cost.
- Tang, Jie,Liu, Xirong,Zeng, Chunlin,Meng, Hao,Tian, Mi,Guo, Cancheng
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p. 266 - 270
(2017/06/19)
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- A betamethasone ring oxygen water peptide synthesis method
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The invention belongs to the field of steroid hormone drug synthesis, and particularly relates to a synthesis method of a betamethasone epoxy hydrolyzate, which comprises the following step: by using a betamethasone suppressor as a raw material, carrying out bromohydroxylation reaction and epoxy hydrolysis reaction to obtain the betamethasone epoxy hydrolyzate finished product, thereby enhancing the overall yield of the betamethasone epoxy hydrolyzate by reducing the elutriation running. The method reduces the hydrolysis of the bromohydroxy substance in the reaction, and integrates the steps of epoxidation and hydrolysis into one step, thereby enhancing the yield of the betamethasone epoxy hydrolyzate.
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Paragraph 0016; 0049; 0053; 0054
(2017/06/02)
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- Process improvements in the synthesis of corticosteroid 9,11β-epoxides
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Corticosteroid 9,11β-epoxides are key intermediates in the preparation of pharmaceutically important compounds such as betamethasone, mometasone, beclomethasone, and dexamethasone. A new process for the 9,11β-epoxide was developed using a PCl5-mediated regioselective dehydration of 11α-hydroxy-steroid to form the corresponding Δ9,11 double bond. The olefin is then converted into 9α,11β-bromoformate by treatment with 1,3-dibromo-5, 5-dimethyl hydantoin (DBH) in DMF and subsequently cyclized to produce the desired 9,11β-epoxide upon treatment with NaOH. Major process-related impurities such as 21-OH-Δ9,11-triene, 21-OH-Δ11,12-triene, 21-Cl-Δ9,11-triene, and β-epoxide-21-cathylate as well as 11β-Cl are all eliminated or minimized. This new process has been implemented in our manufacturing facility in full-scale production and proved to raise the overall yield and the quality of the product dramatically compared to the existing process.
- Fu, Xiaoyong,Tann, Chou-Hong,Thiruvengadam
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p. 376 - 382
(2013/09/07)
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