PRACTICAL SYNTHESIS OF CODEINE FROM DIHYDROTHEBAINONE

The conversion of dihydrothebainone to codeine or thebaine is achieved in high yield. Bromination and dehydrobromination construct the 4,5-oxide bridge to give 1-bromo- and 1,7-dibromodihydrocodeinone which yield dihydrocodeinone practically quantitatively after catalytic debromination. Ketalization and acid-catalyzed elimination of methanol give excellent yields of .DELTA.6-dihydrothebaine to which is added methyl hypobromite using N-bromoacetamide in methanol. The action of potassium tert-butoxide in Me2SO on the resulting 7-bromodihydrocodeinone dimethyl ketal gives codeinone dimethyl ketal selectivity at 60.degree. while at 120.degree. thebaine is the exclusive product. Hydrolysis to codeinone and borohydride reduction give codeine in 70% overall yield. The bromo intermediates in the formation of the 4,5-oxide bridge is examined. 1,5.beta.,7.alpha.-Tribromodihydrothebainone is identified as the main product in the tribromination of dihydrothebainone.