反应详情

温度

-30 °C

4-(3-Fluoro-benzyl)-7-hydroxy-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester (15) (60 g, 0.17 mol) was dissolved in 600 mL anhydrous DMF under a blanket of argon and cooled to −30° C. Oxalyl chloride (40.7 mL, 0.47 mol) was then added very slowly (producing a large volume of gas), with the reaction vessel open to the atmosphere. The solution was then heated to 75° C. for 2 hours. The solution was cooled to room temperature and poured into a solution of 150 g. NaCl in 6 L ice water without stirring. The mixture was allowed to sit without stirring for 15 minutes, and was then stirred vigorously for 1 minute with a spatula. The precipitated solid product was collected by vacuum filtration to yield 55 g (87% yield) of 7-chloro-4-(3-fluoro-benzyl)-5-oxo-4,5-dihydro-thieno[3,2-b]pyridine-6-carboxylic acid ethyl ester. 1H-NMR (DMSO-d6) δ 1.30 (t, J=7.2 Hz, 3H), 4.34 (q, J=7.2 Hz, 2H), 5.45 (s, 2H), 7.06-7.17 (m, 3H), 7.37 (m, 1H), 7.49 (d, J=5.6 Hz, 1H), 8.20 (d, J=5.6 Hz, 1H) ppm; EIMS m/z 366 (M+1).

1. customproducing a large volume of gas), with the reaction vessel open to the atmosphere
2. temperatureThe solution was then heated to 75° C. for 2 hours
3. temperatureThe solution was cooled to room temperature
4. additionpoured into a solution of 150 g
5. stirringwas then stirred vigorously for 1 minute with a spatula
6. filtrationThe precipitated solid product was collected by vacuum filtration