METHYL 4-(4-BROMOPHENYL)THIOPHENE-2-CARBOXYLATE synthesis

Yield:26137-07-5 40%

Reaction Conditions:

Stage #1: methyl 4-(4-aminophenyl)thiophene-2-carboxylatewith hydrogen bromide;sodium nitrite in water at 0; for 1 h;
Stage #2: with hydrogen bromide;copper(I) bromide in water at 0; for 1 h;

Steps:

6.3

0.6 ml of concentrated hydrobromic acid is added to a solution of 103 mg of the product obtained in stage 2 above in 1.5 ml of water. The reaction medium is cooled to 0°C and a solution of 35.5 mg of sodium nitrite (1.1 equivalents) in 0.5 ml of water is then added dropwise. After stirring for 1 hour at 0°C, a solution of 68 mg of copper bromide in 0.5 ml of concentrated hydrobromic acid is added dropwise. The reaction medium is stirred for a further 1 hour at 0°C and then diluted with ethyl acetate (30 ml), washed with water (3X15 ml), washed with saturated sodium hydrogen carbonate solution (15 ml) and then washed again with water (15 ml). The organic phase is dried over sodium sulphate, filtered and then concentrated under reduced pressure. Chromatography of the residue on silica gel (95/5 cyclohexane/ethyl acetate) allows 52 mg of the desired product to be isolated. Yield: 40% 'H NMR (CDC13) 8 (PPM) : 3.92 (s, 3H), 7.45 (d, 2H), 7.55 (d, 2H), 7.65 (s, 1H), 8.05 (s, 1H) HPLC: 91.4%

References:

WO2005/3115,2005,A1 Location in patent:Page/Page column 30