GB620258A - Improvements in or relating to the manufacture of hydro-phenanthrene derivatives - Google Patents

Abstract

Octahydrophenanthrenes are prepared by reacting a 5 : 6 : 7 : 8-tetrahydroisoquinoline-halogenomethylate with a benzyl magnesium halide, hydrogenating the resulting 1-benzyl-2-methyl-hexahydroisoquinoline to the corresponding octahydroisoquinoline, and ring closing the latter by heating with phosphoric acid. The benzyl magnesium halide has the formula <FORM:0620258/IV (b)/1> where one at least of X1 is a lower saturated alkyl or alkoxy group and the other symbols X1 are hydrogen or a lower saturated alkyl or alkoxy group. The final 1-methyl-piperido-(21 : 31 : 41 : 9 : 14 : 13)-5 : 6 : 7 : 8 : 9 : 10 : 13 : 14-octahydrophenanthrene has the formula <FORM:0620258/IV (b)/2> where X is hydrogen or the same as X1, or the product of transformation thereof during the process, e.g. OH in place of OMe. In the examples, 5 : 6 : 7 : 8-tetrahydroisoquinoline-iodomethylate and -bromomethylate are prepared from 1 : 3-dihydroxy - 5 : 6 : 7 : 8 - tetrahydroisoquinoline by reaction with phosphorus oxychloride to give 1 : 3-dichloro-5 : 6 : 7 : 8-tetrahydroisoquinoline, followed by hydrogenation to 5 : 6 : 7 : 8-tetrahydroisoquinoline and treatment of the latter with methyl iodide or bromide. The halogenomethylates are then treated with 3 : 4-dimethylbenzyl magnesium chloride and m- and p-methoxybenzyl magnesium bromides to give the corresponding piperido-octahydrophenanthrenes after hydrogenation followed by ring - closure. When present, the bulk of any methoxyl group is hydrolysed to hydroxyl in the final cyclization with phosphoric acid. According to the Provisional Specification, this hydroxyl group may be remethylated with methyl sulphate.