Anisole → Tolmetin

Participants

Reaction Conditions

Reaction Steps

To a solution of the Grignard reagent prepared from 0.71 g. (31 mmol) of magnesium and 5.3 g. (31 mmol) of 4-bromotoluene in a mixture of 20 ml. of anisole and 5 ml. of tetrahydrofuran was added over five minutes with stirring and heating a solution of 0.98 g. (6.0 mmol) of 5-cyano-1-methylpyrrole-2-acetic acid in a mixture of 5 ml. of anisole and 3 ml. of tetrahydrofuran. The reaction mixture was then heated under reflux (115° C.) for two hours, cooled, and partitioned between ether and dilute aqueous hydrochloric acid. Following a work-up procedure similar to that described for Example 1, there was obtained from the ether phase 60 mg. of purple liquid that contained only a trace of starting cyanoacid, and from the aqueous phase, 1.18 g. (77% yield) of 1-methyl-5-p-toluoylpyrrole-2-acetic acid as a brown solid.

Provenance & Evidence