Triethylamine → 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide

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Reaction Steps

Oxalyl chloride (9.2 ml) was added dropwise at 0° C. to a stirred suspension of 4-chlorobenzo[b]thiophene-2-carboxylic acid (17.89 g) in dichloromethane (240 ml), then the mixture was allowed to warm to ambient temperature. Dimethylformamide (8 drops) was added and the mixture was stirred at ambient temperature for 4 hours. The dichloromethane was removed in vacuo and tetrahydrofuran (200 ml) and dichloromethane (50 ml) were added to the residue to give a solution. N,O-Dimethylhydroxylamine hydrochloride (9.03 g) and triethylamine (25 ml) were added and the mixture was stirred at ambient temperature for 18 hours. Water (50 ml) and triethylamine (10 ml) were added then the solution was stirred at ambient temperature for 1 hour and diluted with water (1000 ml). The product was extracted into dichloromethane (3×300 ml), the combined extracts were dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash chromatography over silica using a 19:1 mixture of dichloromethane and methanol as eluant. Appropriate fractions were combined and the solvents removed in vacuo to leave 4-chloro-N-methoxy-N-methylbenzo[b]thiophene-2-carboxamide (19.7 g) as an off-white solid which was used without further purification.

Provenance & Evidence