Yield:57248-14-3 100%

Reaction Conditions:

with oxalyl dichloride;N,N-dimethyl-formamide in dichloromethane at 20; for 2.5 h;

Steps:

1 Preparation 1. 2,5-dichlorothiophene-3-carbonyl chloride

To a suspension of 2,5-dichloro-thiophene-3-carboxylic acid (49.7 g; 252.23 mmoles; 1.00 equiv) in dichloromethane (500 mL), add dimethylformamide (0.5 mL; 6.47 mmoles) followed by a solution of 2 M oxalyl chloride in dichloromethane (138.73 mL; 277.45 mmoles; 1.1 equiv) over 1.5 hr. (vent the evolved gas through a caustic solution). Stir the resulting clear solution at room temperature for 1 hr. until gas evolution has ceased and the reaction is complete by LCMS (quench a sample into 7 M NH₃/MeOH for reaction monitoring) MS (m/z): = 195.9, 197.9 (M+H)⁺ forcorresponding primary amide. Evaporate to dryness to give the title intermediate as a brown oil (55 g, 252 mmol, quantitative).

References:

WO2013/9517,2013,A1 Location in patent:Page/Page column 5; 6