HCID 54467457, compound → HCID 20701006, compound
Reaction equation
[OH:1]C1C=CC2[C@H]3CC[C@H]4[C@H]([C@@H]3CCC=2C=1)CCC4.[CH3:19][O:20][C:21]1[CH:37]=[CH:36][C:35]2[C@H:27]3[CH2:28][CH2:29][C@H:30]4[C@H:34]([C@@H:26]3[CH2:25][CH2:24][C:23]=2[CH:22]=1)[CH2:33][CH2:32][CH2:31]4>>[CH3:19][O:20][C:21]1[CH:37]=[CH:36][C:35]2[C@H:27]3[CH2:28][CH2:29][C@H:30]4[C@H:34]([C@@H:26]3[CH2:25][CH2:24][C:23]=2[CH:22]=1)[CH2:33][CH2:32][C:31]4=[O:1]Participants
Procedure
The 7α-substituted gon-4-en-3-one thus obtained can be aromatized to the 3-hydroxygona-1,3,5(10)-triene [Yuan, S.-S. et al, Steroids 39, 279 (1982)] which then can be methylated to the 3-methoxy derivative. Conversion to a 3-methoxygona-1,3,5(10)-triene can also be achieved directly [Brito, M. et al, Synth. Commun. 26, 623 (1996)]. When R6 is (17α-H,17β-OR7), the 17-hydroxy group is deprotected and oxidized to produce a 3-methoxygona-1,3,5(10)-trien-17-one derivative [for oxidation reactions, see: Hudlicky, M., Oxidations in Organic Chemistry, ACS Monograph 186, Washington, D.C., 1990]. When R6 is (17α-C≡CH,17β-OR7), the 17-hydroxy group is again deprotected and the 17α-ethynyl-17β-hydroxy derivative is converted to the 17-ketone e.g. by reaction with silver carbonate on celite [Rao, P. N. et al, Steroids 59, 621 (1994)] or other methods known in the art. In both cases, conversion to the 17-ketone can also be accomplished prior to aromatization. The 3-methoxygona-1,3,5(10)-trien-17-one derivative thus obtained can be brominated directly, for instance by reaction with copper(II) bromide in benzene/methanol [Segaloff, A. et al, Steroids 22, 99 (1973)]. The 3-methoxygona-1,3,5(10)-trien-17-one derivative can also be converted to the enol acetate and then treated with bromine [Johnson, W. S. et al, J. Am. Chem. Soc. 79, 2005 (1957)], or to the enol silyl ether followed by reaction with e.g. N-bromosuccinimide [Heathcock, C. H. et al, J. Amer. Chem. Soc. 104, 6081 (1982)]. Dehydrobromination of the 16α-bromoketone, e.g. by reaction with LiBr/Li2CO3/DMF [Bull, J. R. et al, J. Chem. Soc., Perkin Trans. I, 241 (1990)], usually results in a mixture of (14β)-3-methoxygona-1,3,5(10),15-tetraen-17-one and 3-methoxygona-1,3,5(10),14-tetraen-7-one derivatives. They can be separated whereafter the latter is reduced to the corresponding (17β)-3-methoxygona-1,3,5(10),14-tetraen-17-ol derivative by use of sodium borohydride, lithium aluminium hydride or other reducing agents.
Sources & evidence
- ORD record
- ord-0e30dec2821b4745b347747b802383f3
- Source dataset
- uspto-grants-2004_08
- Patent number
- US06780854B2
Reaction notes
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