Novel Friedel—Crafts Alkylation of Estrogens in the Presence of Anhydrous FeCl₃ or FeCl₃—Graphite as Catalyst.

Targeting RORs nuclear receptors by novel synthetic steroidal inverse agonists for autoimmune disorders

“…Finally, compound 18 was reacted with NaSCH 3 in DMF 34 in comparison with compound 6 (schemes 1 and 2) towards NaSCH 3 has not been understood. In this case, the F-C acylation reaction of 3-methoxy-estrone, as for some reported alkylation 35 other than with adamanthanol, was proved not to be a regio-specific reaction. Therefore, it is possible to conclude that the lack of region specificity of F-C acylation towards position 2 together with the low yields of compound 19a might represent a drawback for the future synthesis of novel 2substituted analogs.…”

“…34 Accordingly, by comparing the two synthetic pathways (scheme 1 and 2), it was concluded that by the pathway in scheme 2 the scope to facilitate the synthetic work was achieved, but despite the laborious work up, the pathway in scheme 1 was undoubtedly the more advantageous because of the higher yields. h. 35 In this case, a mixture of three compounds was obtained that were separated by Flash Chromatography. As expected, due to the more electron-rich position 2, the 2-benzoyl-3-methoxyderivative 14a was retrieved in greater amount (58%), the 4-benzoyl-methoxy isomer 14b (31%) and in lesser amount the 2-benzoyl-3-hydroxy derivative 14c (2%).…”