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
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.
Full text doi:10.1071/C97179
© CSIRO 1998