Synthesis of morphine‐[ N ‐methyl‐ 14 C]‐6‐ β ‐ D ‐glucuronide

Protected morphine‐6‐glucuronide was converted into morphine‐[ N ‐methyl‐ 14 C]‐6‐glucuronide by a three‐step procedure. Methyl (3‐pivaloylmorphin‐6‐yl 2,3,4‐tri‐ O ‐isobutyryl‐ β ‐D‐glucopyranosid)uronate was N‐demethylated by treatment with 1‐chloroethyl chloroformate to afford protected normorphine‐6‐glucuronide as its hydrochloride salt. The normorphine‐6‐glucuronide derivative was alkylated with iodomethane‐[ 14 C] in the presence of potassium carbonate to produce C‐14 labelled protected morphine‐6‐glucuronide. Finally, hydrolysis of the protecting groups using 5% sodium hydroxide solution gave morphine‐[ N ‐methyl‐ 14 C]‐6‐ β ‐D‐glucuronide with a specific activity of 41.8 mCi mmol −1 and radiochemical purity of 99.2% (HPLC). Copyright © 2002 John Wiley & Sons, Ltd.