Methyl iodide → 3-Methoxybenzoic Acid

Participants

Reaction Steps

To a mixture of diisopropylamine (2.92 ml) and tetrahydrofuran (17.5 ml), at -78°, under nitrogen, was added 1.17 M n-butyllithium (16.3 ml). After stirring for 15 min, a solution of 4-[5-[3-(dimethylcarbamoyl)propyl]-1-propylindol-3-ylmethyl]-3-methoxybenzoic acid (3.8 g) in tetrahydrofuran (50 ml) was added. The reaction was allowed to warmed to -30° and stirred for 45 min. Methyl iodide (2.71 ml) was added and the mixture stirred for 90 min. The reaction was quenched with saturated ammonium chloride (100 ml) and the organic layer was partitioned between ethyl acetate and saturated ammonium chloride. The organic phase was washed (saturated ammonium chloride, water), dried (MgSO4), and evaporated. The residue was dissolved in saturated sodium bicarbonate. The solution was washed with diethyl ether and acidified to pH 2 with 6N hydrochloric acid. The product was extracted into ethyl acetate, and the organic layer was dried (MgSO4) The solvent was evaporated and the residue was triturated with hexane, powderized and vacuum dried at 40° for 18 hr to afford 4-[5-[3-dimethylcarbamoyl)butyl]1-propylindol-3-ylmethyl]-3methoxybenzoic acid (2.95 g, 75%) as a pale pink solid; mp 60.0°-64.0°.

Provenance & Evidence