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Synlett 2007(14): 2185-2188  
DOI: 10.1055/s-2007-984908
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Alkylation of 7-Hydroxy-DHEA Derivatives

Peter G. M. Wuts*, Nicholas Duda
Pfizer Global Research and Development, Ann Arbor, MI 48105, USA
Fax: +1(734)6223294; e-Mail: peter.g.wuts@pfizer.com;
Further Information

Publication History

Received 25 April 2007
Publication Date:
20 July 2007 (online)

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Abstract

A series of 7-hydroxysteroids were stereoselectively alkylated with a variety of electron-rich nucleophiles to give 7-α-substituted steroids.

Key words

alkylations - steroids - Lewis acids - stereoselective - eliminations

    References and Notes

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4

Nomenclature: 13a refers to the product 13 with the a nucleophile at the 7-position.

8

The Multimax is a device used to monitor reactions by heat flow. This is accomplished by comparing the system’s jacket temperature (Tj) and the reaction temperature (Tr). Tr-Tj when plotted in real time gives a measure of the course of the reaction.

11

Typical Experimental A solution of diacetate 1 (2.0 g, 5.15 mmol) and 2-methyl-furan (2.0 mL) in 20 mL of MeCN was equilibrated to 20 °C in the Mettler Multimax. Then Sc(OTf)3 (200 mg, 0.46 mmol) was added. The reaction was monitored by observing the Tr-Tj profile and by TLC (50% EtOAc-hexane). After complete reaction, H2O was added to the mixture and the product isolated with EtOAc. Crystallization from EtOAc-hexane afforded 1.71 g of product. The mother liquors were chromatographed on silica gel with 25% EtOAc-hexane to afford an additional 350 mg for a total of 97% yield.