反应详情

温度

2 °C

A mixture of 3-methylbenzofuran-2-carboxylic acid (1.0 kg, 5.676 mol) in methylene chloride (5.8 L) and DMF (5 mL) was chilled to ˜2° C. A solution of oxalyl chloride (864 g, 6.81 mol) was added to the reaction mixture keeping the temperature below 10° C., over a period of 2 hrs. A vigorous evolution of a gas was observed. The reaction mixture was stirred overnight under nitrogen at room temperature and then refluxed for 3 hrs. All of the solids were dissolved to give a brown color solution. HPLC analysis of an aliquot indicated that the reaction was complete. The mixture was concentrated on a rotary evaporator and the residual oxalyl chloride was chased with DCM (2 L). The solid product was re-dissolved in DCM (6 L) in a round bottom flask (10 L) and chilled to ˜−5° C. A solution of methyl amine (40% in water, 1.7 L, 3.5 eq, 19.86 mol) was carefully added to the acid chloride solution while keeping the temperature below 8° C. then stirred overnight at room temperature. Analysis of an aliquot indicated that the reaction was complete. Water (8.0 L) was added to the reaction mixture, the layers were separated, the aqueous layer was back extracted with DCM (2×3 L), the combined organic layer was washed with water (4 L) and dried over Na2SO4. The organic layer was filtered, the filtrate was concentrated and traces of DCM were co evaporated with heptanes (2 L). The heptanes slurry was filtered and the cake was washed with heptanes (2×2 L). All the brown color was removed in the heptane filtrate. The solid product was dried under high vacuum overnight to a constant weight. Yield of the title compound was 1.015 kg (94.5%. 1H NMR {CDCl3}: δ (ppm) 8.45 (s, 1H), 7.61 (d, 1H), 7.41 (m, 2 H), 7.30 (m, 1 H), 3.03 (d, 2 H), 2.63 (s, 3 H). HPLC: 99.0 area % (RT=7.91 min)

1. customthe temperature below 10° C.
2. temperaturerefluxed for 3 hrs
3. dissolutionAll of the solids were dissolved
4. customto give a brown color solution
5. concentrationThe mixture was concentrated on a rotary evaporator
6. dissolutionThe solid product was re-dissolved in DCM (6 L) in a round bottom flask (10 L)
7. temperaturechilled to ˜−5° C
8. customthe temperature below 8° C.
9. stirringthen stirred overnight at room temperature
10. customthe layers were separated
11. extractionthe aqueous layer was back extracted with DCM (2×3 L)
12. washthe combined organic layer was washed with water (4 L)
13. dry with materialdried over Na2SO4
14. filtrationThe organic layer was filtered
15. concentrationthe filtrate was concentrated
16. customtraces of DCM were co evaporated with heptanes (2 L)
17. filtrationThe heptanes slurry was filtered
18. washthe cake was washed with heptanes (2×2 L)
19. customAll the brown color was removed in the heptane filtrate
20. customThe solid product was dried under high vacuum overnight to a constant weight