Norcodeine hydrochloride

A solution of 6-acetylcodeine (10.0 g, 29.3 mmol), 1-chloroethyl chloroformate (5.56 g, 38.1 mmol), and proton sponge (1.0 g) in methylene chloride (50 ml) was heated at reflux for 50 min. The reaction mixture was evaporated in vacuo to about 30 ml. Methanol (25 ml) and concentrated HCI (2 ml) were added. The solution was heated at reflux for 40 min. and evaporated in vacuo to almost dryness. The residue was added hexane and filtered to give norcodeine hydrochloride (8.8 g, 93% yield). 

A mixture of norcodeine hydrochloride (11.48 g, 27.8 mmol), (chloromethyl)cyclopropane (5.14 g, 55.6 mmol), sodium carbonate (14.73 g, 139.0 mmol), and potassium iodide (4.61 g, 27.8 mmol) in ethanol (250 ml) was heated at reflux for 20 hr, cooled, and evaporated in vacuo to dryness. The residue was basified with NH4OH, and extracted with methylene chloride. The extract was washed with water and evaporated in vacuo to dryness. The residue (11.7 g) was chromatographed on silica gel with a eluting solvent system of methanol/ethyl acetate (10/90) to give 17-cyclopropylmethylnorcodeine (10.68 g, 91% yield). 

A patent has been published that covers the rearrangement of ethers of morphine and N-alkyl-normorphines to the corresponding derivatives of apomorphine and N-alkyl-norapomorphines by phosphoric acid at 125— 140 lO-Oxomorphine has been isolated as an oxidation production from solutions of morphine hydrochloride/ and morphine has been shown to be converted into morphine N-oxide and normorphine by guinea-pig liver microsomal preparations, which convert codeine, under similar conditions, into codeine AT-oxide, norcodeine, morphine, and normorphine/ ... 

Norcodeine [467-15-2] M 285.3, m 185°, 186°, pK ° 9.10. It crystallises from acetone or ethyl acetate. [Speyer Walther ChemBer 63 822 7950.] Tlhe hydrochloride itas m 309°(dec) when crystallised from H2O. 

---