反应详情

温度

140 °C

To a stirred solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (500 mg, 1.6 mmol), N-ethyldiisopropylamine (1.04 g, 2.0 mmol) and 1-hydroxybenzotriazole hydrate (40 mg, 0.3 mmol) in DMF (16 mL) at ambient temperature and under argon was added 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (517 mg, 1.6 mmol) followed by N-hydroxymethylacetamidine (149 mg, 2.0 mmol). After 14 h the mixture was diluted with water (15 mL) and extracted with EtOAc (3×25 mL). The combined extracts were washed with 10% aqueous LiCl solution (2×10 mL) then dried over sodium sulfate, filtered and concentrated. The residue was then dissolved in DMF (16 mL) and heated at 140° C. for 3 h then cooled, diluted with EtOAc (60 mL), washed with 10% aqueous LiCl (3×100 mL), then dried over sodium sulfate, filtered and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate 8:2 to 0:1) afforded the title compound (385 mg, 69%) as a yellow solid. MS: m/e=349.4 [M+H]+.

1. extractionextracted with EtOAc (3×25 mL)
2. washThe combined extracts were washed with 10% aqueous LiCl solution (2×10 mL)
3. dry with materialthen dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. dissolutionThe residue was then dissolved in DMF (16 mL)
7. temperaturethen cooled
8. additiondiluted with EtOAc (60 mL)
9. washwashed with 10% aqueous LiCl (3×100 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customPurification by chromatography (SiO2, heptane:ethyl acetate 8:2 to 0:1)