反应详情

A solution of phosphorous oxychloride (3.21 ml, 34.5 mmol) was added dropwise over a period of 15 min to a 0° C. solution of DMF (2.67 ml, 34.5 mmol) under nitrogen. The mixture was allowed to warm to RT and stirred for 30 min. Dichloroethane (20 mL) was added and the reaction mixture cooled to 0° C. A solution of methyl 3-chloro-1H-pyrrole-2-carboxylate (5 g, 31.3 mmol) in dichloroethane (20 mL) was added dropwise over 30 min. The reaction mixture was warmed to RT and allowed to stir for 1 h. The flask was placed in an oil bath at 90° C. and stirred for 30 min. The reaction mixture was cooled to RT, a solution of sodium acetate (25 g, 305 mmol) in water (25 mL) was added and stirred for 15 min. Methylene chloride (100 mL) was added and the layers separated. The aqueous layer was extracted with methylene chloride (2×25 mL), the organic layers were combined, dried over sodium sulfate, filtered and evaporated. The crude material was purified by column chromatography (hexanes: EtOAc; 10-100%) to afford three isolated materials. The first compound to elute was a mixture of starting materials and product. The second fraction to elute was evaporated and recrystallized from a minimal amount of EtOAc to afford methyl 3-chloro-5-formyl-1H-pyrrole-2-carboxylate (1.2 g, 6.40 mmol, 20% yield) as yellowish crystals. The third fraction to elute was evaporated and recrystallized from hexanes: EtOAc to afford methyl 3-chloro-4-formyl-1H-pyrrole-2-carboxylate (1.05 g, 18% yield) as a tan solid. Methyl 3-chloro-5-formyl-1H-pyrrole-2-carboxylate: 1H NMR (400 MHz, DMSO-d6): 6 ppm 14.0 (br. s., 1H), 9.64 (d, 1H) 7.01 (s, 1H) 3.82 (s, 3H). MS: m/z 188.0 (M+1). Methyl 3-chloro-4-formyl-1H-pyrrole-2-carboxylate: 1H NMR (400 MHz, DMSO-d6): 6 ppm 14.0 (br. s., 1H) 9.77 (s, 1H) 7.77 (s, 1H) 3.80 (s, 3H). MS: m/z 188.0 (M+1).

1. temperaturethe reaction mixture cooled to 0° C
2. temperatureThe reaction mixture was warmed to RT
3. stirringto stir for 1 h
4. customThe flask was placed in an oil bath at 90° C.
5. stirringstirred for 30 min
6. temperatureThe reaction mixture was cooled to RT
7. stirringstirred for 15 min
8. customthe layers separated
9. extractionThe aqueous layer was extracted with methylene chloride (2×25 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. customevaporated
13. customThe crude material was purified by column chromatography (hexanes: EtOAc; 10-100%)
14. customto afford three isolated materials
15. washThe first compound to elute
16. additiona mixture of starting materials and product
17. washThe second fraction to elute
18. customwas evaporated
19. customrecrystallized from a minimal amount of EtOAc