反应详情

温度

20 °C

Dimethylformamide (230 mL, 3.13 mol) and 1200 mL of dichloromethane were cooled to 4° C. and 222 mL of phosphorus oxychloride was added with stirring. The temperature increased to 20° C. The mixture was cooled to 2° C. (2,4-Dimethyl-1H-pyrrol-3-yl)-acetic acid (240 g, 1.57 mol) was slowly added. The mixture was refluxed for 20 minutes. Thin layer chromatography (ethyl acetate:hexane:acetic acid 4:6:0.5) showed no starting material at Rf 0.7 and a heavy spot at the origin. The mixture was cooled to 5° C. and 1200 mL of ice water were added. The maximum temperature reached was 30° C. The mixture was stirred in an ice bath for 30 minutes. The dichloromethane layer was separated and discarded. The aqueous layer was cooled to 9° C. and adjusted to pH 12 with about 1650 mL of 9 N potassium hydroxide. The maximum temperature reached was 50° C. The mixture was cooled in an ice bath and adjusted to pH 3 with about 800 mL of 10 N hydrochloric acid. The solids were collected by vacuum filtration, washed three times with 300 mL of water each time and air dried to give 274 g (96% yield) of (5-formyl-2,4-dimethyl-1H-pyrrol-3-yl)-acetic acid as a brown solid. 1H-NMR (dimethylsulfoxide-d6) δ 2.15, 2.18 (2×s, 2×3H, 2×CH3), 3.28 (s, 2H, CH2), 9.44 (s, 1H, CHO), 11.50 (s, 1H, pyrrole NH), 12.07 (s, 1H, COOH). MS m/z 182, [M+1].

1. additionwas slowly added
2. temperatureThe mixture was refluxed for 20 minutes
3. temperatureThe mixture was cooled to 5° C.
4. customreached was 30° C
5. stirringThe mixture was stirred in an ice bath for 30 minutes
6. customThe dichloromethane layer was separated
7. temperatureThe aqueous layer was cooled to 9° C.
8. customreached was 50° C
9. temperatureThe mixture was cooled in an ice bath
10. filtrationThe solids were collected by vacuum filtration
11. washwashed three times with 300 mL of water each time and air
12. customdried