6-Methylbenzo[b]thiophene-2-carboxylic acid

Synthesis

34576-96-0

7440-44-0

1467-86-3

Example 17 Synthesis of 6-methylbenzo[b]thiophene-2-carboxylic acid (1) (Method C) (MeOH/water and ammonium formate) Procedure: a suspension of palladium in 5% wet charcoal (50% water, 1.065 g) and ammonium formate (2.52 g) in methanol (30 ml) was stirred for 20 minutes under inert atmosphere. Subsequently, a solution consisting of 2.52 g of ammonium formate in 5 ml of water and a solution consisting of 2.26 g of 3-chloro-6-methylbenzo[b]thiophene-2-carboxylic acid (18), 70 ml of methanol and 10 ml of 1N NaOH were added. The reaction mixture was stirred at reflux for 15 hours under inert atmosphere. After that, 0.425 g of Pd/C (5% wet) was added and the reaction mixture was continued to reflux for 24 hours. Upon completion of the reaction, the mixture was cooled, diluted with methanol, filtered through a bed of diatomaceous earth and the catalyst was further washed. The filtrate was evaporated to dryness under reduced pressure and the residue was treated with 70 ml of 1N HCl and 250 ml of ethyl acetate. The organic phase was washed three times with brine and evaporated to dryness to give 1.82 g of the target compound (1) as a white solid; the HPLC purity was 98.2% and the yield was 94.7%.

References