Trityl chloride → 4-Iodo-1-tritylimidazole

Participants

Reaction Steps

As depicted in Scheme II, imidazole was reacted with iodine under basic conditions at reduced temperature in an appropriate solvent, yielding a mixture of iodoimidazoles (v), for example, 2,4,5-triiodoimidazole and 2,5-diiodoimidazole. The mixture of iodoimidazole derivatives (v) was then treated with aqueous sodium sulfite at elevated temperature in an appropriate solvent, yielding a single iodo derivative (vi), for example, 5-iodoimidazole. The free amine in the 1-position of the iodoimidazole (vi) ring was then protected by reacting it with triphenylmethyl chloride under basic conditions in an appropriate solvent, affording the corresponding 1-(triphenylmethyl)-4-iodoimidazole (vii). The iodoimidazole (vii) was in turn treated with ethylmagnesium bromide in an appropriate solvent, then reacted with an appropriate cyclic ketone (ii), for example, 6-methoxy-5-methylindan-1-one (X is —CHR17—), affording the corresponding 1,2-unsaturated heterocyclic derivative (viii), for example, 3-(imidazol-5-yl)-5-methoxy-6-methylindene. Heterocyclic derivative (viii) was then hydrogenated under conditions set forth above, yielding the corresponding compounds of formula (I), for example, 1-(imidazol-5-yl)-6-methoxy-5-methylindane. Example 4 set forth below provides in detail the synthesis route shown in Scheme II.

Provenance & Evidence