Stereoselective alkylation of 7-hydroxy-DHEA derivatives

Synlett

Volumn , Issue 14, 2007, Pages 2185-2188

  Wuts, Peter G M ^a   Duda, Nicholas ^a  

^a PFIZER INC   (United States)

Author keywords

Alkylations; Eliminations; Lewis acids; Stereoselective; Steroids

Indexed keywords

7 HYDROXY DEHYDROEPIANDROSTERONE; PRASTERONE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; ELECTRON; STEREOCHEMISTRY; SUBSTITUTION REACTION;

EID: 34548788987     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2007-984908     Document Type: Article

References (13)

1. Rabasseda, X.; Silvestre, J.; Castañer, J. Drugs Future 1999, 24, 488.
2. McMahon, E. G. Curr. Opin. Pharmacol. 2001, 1, 190.
3. For similar reactions on simple nonsteroidal substrates, see: (a) Pearson, W. H.; Schkeryantz, J. M. J. Org. Chem. 1992, 57, 2986.
4. (b) Malkov, A. V.; Davis, S. L.; Baxendale, I. R.; Mitchell, W. L.; Kocovsky, P. J. Org. Chem. 1999, 64, 2751.
5. (c) Malkov, A. V.; Davis, S. L.; Baxendale, I. R.; Mitchell, W. L.; Kocovsky, P. J. Org. Chem. 1999, 64, 2764.
6. Nomenclature: 13a refers to the product 13 with the a nucleophile at the 7-position.
7. Negi, A. S.; Dwivedy, I.; Roy, R.; Ray, S. Steroids 1995, 60, 470.
8. For an alternative approach to alkylating the 7-position of a steroid with 2-methylfuran, see: Pearlman, B. A.; Padilla, A. G.; Havens, J. L.; Mackey, S. S.; Wu, H. WO 2003082895 A2, 2003.
9. Wuts, P. G. M.; Ashford, S. W.; Anderson, A. M.; Atkins, J. R. Org. Lett. 2002, 5, 1483.
10. j when plotted in real time gives a measure of the course of the reaction.
11. Ha, T. B. T.; Djerassi, C. Tetrahedron Lett. 1985, 26, 4031.
12. For a related process, see: Rueping, M.; Nachtsheim, B. J.; Kuenkel, A. Org. Lett. 2007, 9, 825.
13. 2O 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.