Synthesis of the heteroarotinoid ethyl ( E )‐4‐[2‐(3,4‐dihydro‐4,4‐dimethyl‐2 H ‐1‐benzopyran‐6‐YL)‐1‐ propenyl]benzoate‐ 9,10,11,20‐ 14 C 4

A synthesis of ethyl ( E )‐4‐[2‐(3,4‐dihydro‐4,4‐dimethyl‐2 H ‐1‐benzopyran‐6‐yl)‐1‐propenyl]benzoate‐ 9,10,11,20‐ 14 C4 ( 1 ) is described via a multistep procedure similar to that used to obtained the unlabelled compound 2 . The latter has shown good activity in several assays compared to the standard trans ‐retinoic acid ( 3 ). Treatment of methyl 3‐phenoxypropionate ( 4 ) with methylmagnesium iodide (obtained from H 3 14 C‐I) yielded the labelled tertiary alcohol 5 . Cyclization of the alcohol 5 occurred in the presence of AlCl 3 in nitromethane to give 4,4‐dimethylchroman ( 6 ). Acetylation of 6 with H 3 C 14 C(O)Cl produced ketone 7 labelled at three carbons. Reduction of the carbonyl group in 7 was effected with LiAlH 4 and gave alcohol 8 . Phosphorylation with triphenylphosphine hydrobromide in methanol led to the corresponding phosphonium salt 9 . Addition of n ‐butyllithium to 9 in ether at −78°C generated the expected Wittig reagent in situ , and to this was added labelled ethyl 4‐formylbenzoate [C 2 H 5 O 2 14 C‐C 6 H 4 ‐CHO] ( 10 ). Workup, followed by chromatography of the oily product, afforded a solid. Recrystallization (abs. ethanol) gave 1 which was identical to 2 in terms of spectral data and melting point. The specific activity was determined to be 0.15 μCi/mg.