Diethyl Ether → HCID 21763808, compound

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Reaction Steps

Referring to Scheme I, thebaine (1) is reacted with lithium dimethyl cuprate to provide the 7-methyl-4,5α-epoxy cleaved product, 3,6-dimethoxy-7β,17-dimethyl-4-hydroxy-5,6,8,14-tetradehydromorphinane (2). This compound serves as a useful starting material for the preparation of 7-methyl-3-methoxy-4,5α-epoxy morphinan-6-ones. Thus, to a solution of 1.25 equivalents of lithium dimethyl cuprate, prepared in ether at 0° under inert atmosphere is added a solution of thebaine (1) in benzene or toluene (aromaic hydrocarbon) or methylene chloride (halogenated hydrocarbon) or other suitable inert solvent. The resulting yellow suspension is stirred in the cold for a period of one hour and then poured into a saturated solution of ammonium chloride to quench the reaction. The aqueous phase is adjusted to pH 10 to 13 by use of an inorganic base such as sodium or potassium hydroxide and the organic phase separated. After extraction of the aqueous phase with additional organic solvent, the combined extracts are backwashed, dried and evaporated to a foam. This foam is crystallized from chloroform with the addition of hexane to yield (2) as the monochloroform solvate, mp 98°-101.5°, in about 75% yield.

Provenance & Evidence