PREPARATION OF (R)-11-HYDROXYAPORPHINE DIRECTLY FROM (R)-10,11-DIHYDROXYAPORPHINE ((R)-APOMORPHINE)

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-(isopropylidenyldi oxy)aporphine 5 obtained by the isopropylidenation of apomorphine was regioselectively opened by ten equivalents of trimethylaluminum to giv e (R)-10-hydroxy-11-tert-butyloxyaporphine 6. The free 10-hydroxyl pos ition of 6 was triflated with N-phenyltrifluoromethanesulfonimide and potassium carbonate under reflux to give luoromethyl)sulfonyloxy]-11-t ert-buryloxyaporphine 7. The reduced product, 11-tert-butyloxyaporphin e 8 was prepared from 7 by a palladium-catalyzed hydrogenolysis. The e ther cleavage of (R)-11-tert-butyloxyaporphine with 48% hydrobromic ac id afforded the desired (R)-11-hydroxyaporphine 2 in good yield.