The Conversion of Steroidal Ring B Lactones into Ortho Esters: Preparation of 7,7-Dimethoxy-6-oxaestra-1,3,5(10)-triene Derivatives

David G. Bourke and David J. Collins

Australian Journal of Chemistry 51(11) 1003 - 1018
Published: 1998

Abstract

17β-t-Butyldimethylsilyloxy-3-methoxy-6-oxaestra-1,3,5(10)-trien-7-one (1), prepared in three steps from 17b-hydroxy-3-methoxy-6-oxaestra-1,3,5(10),8-tetraen-7-one (5a), was converted via the corresponding phenolic acid into 1β-t-butyldimethylsilyloxy-5β-(2′-t-butyldimethylsilyloxy-4′-methoxyphenyl)-N,7aβ-dimethyl-N-phenyl-2,3,3aα,4,5,6,7,7a-octahydro-1H-indene-4α-carboxamide (17c). Subjection of (17c) to a reaction sequence with methyl trifluoromethanesulfonate, sodium methoxide/methanol, and then dry methanol/acetic acid gave a low yield (12%) of the ortho ester 3,7,7,17β-tetramethoxy- 6-oxaestra-1,3,5(10)-triene (2b), together with 5β-(2′-hydroxy-4′-methoxyphenyl)-1β-methoxy-N,7aβ-dimethyl-N-phenyl-2,3,3aα,4,5,6,7,7a-octahydro-1H-indene-4α-carboxamide (17e) (29%), 8% of (17a), the 1β-hydroxy analogue of (17e) and 3% of methyl 5-(2′-hydroxy-4′-methoxyphenyl)-1β-methoxy-7aβ-methyl-2,3,3aα,4,5,6,7,7a-octahydro-1H-indene-4α-carboxylate (11c). The outcome of this reaction sequence was complex, and very sensitive to minor changes in conditions. Several related transformations are described, and possible mechanistic pathways are discussed.