A new, practical synthesis of 2-methoxyestradiols
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Pemmaraju N Rao1, James W Cessac
1Department of Organic Chemistry, Southwest Foundation for Biomedical Research, P O Box 760549, 7620 N W Loop 410 (at Military Drive), San Antonio, TX 78227-5301, USA. pnrao@icarus.sfbr.org
Abstract:
An efficient and practical approach to synthesize moderate to large amounts of 2-methoxyestradiol (2-ME2) is described. The key step in the synthesis is the regioselective introduction of an acetyl group at the C-2 position of estradiol using a zirconium tetrachloride mediated Fries rearrangement carried out on estradiol diacetate. The seven step synthetic procedure readily gave 2-ME2 in 49% overall yield. Application of this method to the synthesis of 2-methoxy-7 alpha-methylestradiol is also described.
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