4-Bromotoluene → Tolmetin

Participants

Reaction Steps

To a solution of the Grignard reagent prepared from 0.82 g. (36 mmol) of magnesium and 6.2 g. (36 mmol) of 4-bromotoluene in 15 ml. of anhydrous tetrahydrofuran was added 1.2 g. of solid material which contained about 6.0 mmol of 5-cyano-1-methylpyrrole-2-acetate as the calcium salt and some water which persisted after drying in a vacuum oven. Diphenyl ether (20 g.) was added, and the reaction mixture was heated to remove tetrahydrofuran by distillation until the temperature reached 110° C. The reaction mixture was then heated under reflux 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 130 mg. (13%) of 5-cyano-1-methylpyrrole-2-acetic acid and 970 mg. (yield: 63%, 73% based on unrecovered cyanoacid) of 1-methyl-5-p-toluoylpyrrole-2-acetic acid as brown solids.

Provenance & Evidence