Triethylamine → HCID 67232984, compound

Participants

Reaction Conditions

Reaction Steps

N,N-Dimethylformamide (13 μL) was added to a solution of oxalyl chloride (0.696 mL, 7.97 mmol), 4-bromo-thiophene-2,3-dicarboxylic acid 3-methyl ester and 4-bromo-thiophene-2,3-dicarboxylic acid 2-methyl ester (1.41 g, 5.32 mmol), example 30-c, in tetrahydrofuran (6.4 mL) at 0° C. The reaction mixture was stirred at 0° C. for 15 min, and then at ambient temperature for 1 h. After the reaction mixture was concentrated and dried under hi-vacuum, the residue was dissolved in 1,4-dioxane (2.5 mL) and cooled to 0° C. with an external ice bath. Triethylamine (2.22 mL, 16.0 mmol) and glycine ethyl ester hydrochloride salt (1.11 g, 7.97 mmol) were added slowly to the cold solution. The reaction mixture was warmed to room temperature and stirred for 2.5 h. The reaction mixture was diluted with ethyl acetate and washed successively with 0.5 N HCl, water, saturated sodium bicarbonate solution and brine. The organic solution was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-60% ethyl acetate in hexanes to produce 1.0 g of 4-bromo-2-(ethoxycarbonylmethyl-carbamoyl)-thiophene-3-carboxylic acid methyl ester and 0.1 g of 4-bromo-3-(ethoxycarbonylmethyl-carbamoyl)-thiophene-2-carboxylic acid methyl ester. MS for 4-bromo-2-(ethoxycarbonylmethyl-carbamoyl)-thiophene-3-carboxylic acid methyl ester: (+) m/z 349.9, 351.9 (M+1, 79Br/81Br). MS for 4-bromo-3-(ethoxycarbonylmethyl-carbamoyl)-thiophene-2-carboxylic acid methyl ester: (+) m/z 349.9, 351.9 (M+1, 79Br/81Br).

Provenance & Evidence