Hydrochloric Acid → 5-(4-Chlorophenyl)-3-formylthiophene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a stirred solution 5-(4-chlorophenyl)thiophene-2-carboxylic acid (11 g, 0.046 mol) in dry THF (150 ml) was added n-BuLi (63 ml, 0.102 mol, 1.6 M solution in hexane) in a dropwise manner at −78° C. under inert atmosphere. The temperature was slowly raised to 0° C. over a period of 4 h. The reaction mixture was again cooled to −70° C. and dry DMF (34 ml, 0.43 mol) was added slowly. After completion of the addition of DMF, temperature was raised to −10° C. and stirred for 2 h. The reaction mixture was again cooled to −30° C. and 1.5 N HCl (50 ml) was added slowly and reaction was allowed to come to RT. The reaction mixture was extracted with EtOAc (4×200 ml). The combined organic layer washed with water (2×150 ml), brine (2×150 ml), dried (Na2SO4) and concentrated. The crude product washed with p-ether (100 ml) to afford 8 g of the title compound (65%). Rf=0.2 (CHCl3:MeOH, 8:2). This was found pure enough to carry further. Since this intermediate is unstable it has to be used immediately in the next step.

Provenance & Evidence