56665-79-3Relevant academic research and scientific papers
A regioselective PCl5 mediated dehydration for preparing Δ9,11 corticosteroids
Fu, Xiaoyong,Tann, Chou-Hong,Thiruvengadam,Lee, Junning,Colon, Cesar
, p. 2639 - 2642 (2001)
A regioselective PCl5-induced dehydration of 11α-hydroxy corticosteroids was invented to provide the corresponding Δ9,11 double bond trienes in excellent yield (>90%) with 99:1 regioisomeric ratio to the Δ11,12 isomers. A syn-elimination mechanism was proposed for this reaction.
Process improvements in the synthesis of corticosteroid 9,11β-epoxides
Fu, Xiaoyong,Tann, Chou-Hong,Thiruvengadam
, p. 376 - 382 (2013/09/07)
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.
