- Preparation method of dexamethasone intermediate
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The invention relates to a preparation method of a dexamethasone intermediate. The preparation method comprises the following steps: adding a Grignard reagent and a silylanizing reagent to carry out aGrignard reaction by taking a compound I as an initial raw material and the compound I as a raw material in the presence of a catalyst to obtain a compound II; adding the compound II into a buffer agent and an oxidizing agent for an epoxidation reaction to obtain a compound III; carrying out a ring-opening reaction on the compound III in an acidic environment to obtain a compound IV; and carryingout a hydrolytic reaction on the compound IV in an alkaline environment to obtain the dexamethasone intermediate V. According to the preparation method, the raw material is easily available, the preparation method is simple, and the intermediates in the steps can be directly applied to next reactions without being purified and separated, so that the preparation method is high in yield and suitable for industrial production.
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Page/Page column 8; 11-18
(2019/03/06)
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- Improvements in corticosteroid 21-acetoxy-17α-hydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione synthesis and its use as common intermediate in the synthesis of some impurities related to dexamethasone and mometasone
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There are quite substantial number of impurities related to dexamethasone or mometasone which cannot be made from respective Active Pharmaceutical Ingredients but from common intermediate 21-acetoxy-17α-hydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione (12). As such, a robust and economical synthesis of this key intermediate is important for delivering a resilient and economically viable supply chain for these impurities. Therefore, it is critical to have a robust and economically viable process to synthesize the intermediate 12 in good yield and quality. We report here an improved synthesis of 12 and eight impurities related to dexamethasone and mometasone from this common intermediate.
- Das, Saibal Kumar,Dubey, Manoj Kumar,Buchhikonda, Ravinder
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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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- 16α-methylation process
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Disclosed is a process for the production of a Δ17(20) -steroid of the formula STR1 which comprises starting with a 16-unsaturated corticoid of the formula STR2 and contacting the 16-unsaturated corticoid (I) with a methylating agent in the presence of a copper catalyst and a silylating agent.
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- 16α-methylatedΔ17(20)-corticoids
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C16 -unsaturated corticoids are readily transformed to the corresponding 16α-methyl-17α-hydroxy corticoids by use of a Δ17 (20)-20-silyl ether.
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