Preparation of (R)-11-hydroxyaporphine directly from (R)-10,11- dihydroxyaporphine ((R)-apomorphine)

Article abstract of DOI:10.1002/jhet.5570350307

A Regioselective synthesis of (R)-11-hydroxyaporphine 2 directly from (R)-10,11-dihydroxyaporphine ((R)-apomorphine, 1) is described for the first time. The isopropylidene ketal ring of 10,11-(isopropyl-idenyldioxy)aporphine 5 obtained by the isopropylidenation of apomorphine was regioselectively opened by ten equivalents of trimethylaluminum to give (R)-10-hydroxy-11- tert-butyloxyaporphine 6. The free 10-hydroxyl position of 6 was triflated with N-phenyltrifluoromethanesulfonimide and potassium carbonate under reflux to give (R)-10-[(trifluoromethyl)sulfonyloxy]-11-tert-butyloxyaporphine 7. The reduced product, 11-tert-butyloxyaporphine 8 was prepared from 7 by a palladium-catalyzed hydrogenolysis. The ether cleavage of (R)-11-tert- butyloxyaporphine with 48% hydrobromic acid afforded the desired (R)-11- hydroxyaporphine 2 in good yield.