Reaction of 3-methoxy-17-methylmorphinan-6-one with formaldehyde

Reaction of 3-methoxy-17-methylmorphinan-6-one ( 1 ) and formaldehyde with the presence of calcium hydroxide in aqueous dioxane gave 7,7-bis(hydroxymethyl)-3-methoxy-17-methyl-5-methylenemorphinan-6β-ol ( 2a ). Catalytic reduction of 2a yielded the 5α-methyl compound, 2b . Tosylation of 2a,b followed by lithium triethylborohydride reduction gave either 7α-methyl-6β,7β-oxetanes 4a,b or 7,7-dimethyl-6β-ols 5a,b , depending on reaction conditions. The C-6 ketones 6a,b were prepared by oxidation of 5a,b . One compound in this series, 6a , had antinociceptive activity.