反应详情

A solution of N-allyl-N-(2-bromo-6-fluoro-pyridin-3-yl)-2,2,2-trifluoro-acetamide (3.41 g, 10.43 mmol), palladium acetate (94 mg, 0.42 mmol), tetra(n-butylammonium) chloride (3.19 g, 11.47 mmol) and triethylamine (2.37 g, 23.4 mmol) in anhydrous DMF (20 mL) is stirred at 10° C. under N2 for an hour. DMF is evaporated off and the residue is mixed with water (12 mL) and stirred at rt for an hour. EtOAc (15 mL) is added and stirred at rt overnight. The organic layer is separated and the aqueous layer is extracted with EtOAc (35 mL). The combined organic layer is dried (Na2SO4), filtered, and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 10-60% EtOAc in heptane to afford 5-fluoro-3-methyl-1H-pyrrolo[3,2-b]pyridine (1.5 g) as a solid. MS: 151 (M+H); 1H NMR (300 MHz, CDCl3) δ 2.38(s, 3H), 6.77(d, H), 7.28(s, H), 7.74(dd, H).

1. customDMF is evaporated off
2. additionthe residue is mixed with water (12 mL)
3. additionEtOAc (15 mL) is added
4. stirringstirred at rt overnight
5. customThe organic layer is separated
6. extractionthe aqueous layer is extracted with EtOAc (35 mL)
7. dry with materialThe combined organic layer is dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue is purified by silica gel chromatography
11. washeluting with 10-60% EtOAc in heptane