反应详情

温度

10 °C

Methyl 1H-pyrrole-2-carboxylate (5.78 g, 46.2 mmol) was dissolved in DMSO and cooled to 10° C. NaH was added in two portions over 5 min. The reaction mixture was stirred at 10° C. for 10 min and methyl 6-chloro-5-nitronicotinate (5 g, 23.09 mmol) in DMSO (10 mL) was added slowly over 3 min. The red reaction mixture was allowed to warm to room temperature and stirred overnight. It was cooled to 0° C. and quenched with water (12 mL) and diluted with brine (50 mL). The mixture was washed with EtOAc (2×25 mL) and the aqueous layer was acidified to pH=2 with 4.5 N HCl. It was extracted with EtOAc (1×100 mL) and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo to afford a yellow solid, which was dissolved in MeOH (100 mL) and cooled to 0° C. Thionyl chloride (45 mL, 617 mmol) was added slowly over 5 min. The reaction mixture was stirred at 0° C. for 1 h and then at room temperature overnight. It was concentrated in vacuo and the resulting solid was triturated with ethyl acetate (300 mL). The solid was filtered off and the filtrate was concentrated in vacuo. then washed with ethyl ether to afford methyl 6-(2-(methoxycarbonyl)-1H-pyrrol-1-yl)-5-nitronicotinate (5.04 g, 16.51 mmol, 92% yield) as a yellow solid, [M+H] calc'd for C13H11N3O6, 306; found, 306.

1. customThe red reaction mixture
2. temperatureto warm to room temperature
3. stirringstirred overnight
4. temperatureIt was cooled to 0° C.
5. customquenched with water (12 mL)
6. additiondiluted with brine (50 mL)
7. washThe mixture was washed with EtOAc (2×25 mL)
8. extractionIt was extracted with EtOAc (1×100 mL)
9. dry with materialthe organic layer was dried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto afford a yellow solid, which
13. temperaturecooled to 0° C
14. stirringThe reaction mixture was stirred at 0° C. for 1 h
15. customat room temperature
16. customovernight
17. concentrationIt was concentrated in vacuo
18. customthe resulting solid was triturated with ethyl acetate (300 mL)
19. filtrationThe solid was filtered off
20. concentrationthe filtrate was concentrated in vacuo
21. washthen washed with ethyl ether