反应详情

温度

130 °C

Add PdCl2(PPh3)2 (0.15 g, 0.21 mmol) and Sn(CH3)4 (0.79 mL, 1.02 g, 5.71 mmol) to (R,R)—N-[4-bromo-3-(3-fluoro-4-methoxyphenyl)-isothiazol-5-yl]-2-methylcyclopropanecarboxamide (0.55 g, 1.43 mmol) in DMF (3 mL), and stir the reaction mixture at 130° C. in a sealed tube overnight. Dilute with EtOAc (100 mL) and brine (100 mL). Collect the organic phase, dry (K2CO3) and evaporate. Take up the resultant oil in 1:1 MTBE:KF (aqueous, 15%) (50 mL) and stir at reflux for 1 h. Pour the cooled solution over diatomaceous earth and filter with MTBE (100 mL). Collect the organic phase, dry (K2CO3) and evaporate. Chromatography over silica gel, eluting with 10-30% THF in hexane, affords (R,R)—N-[3-(3-fluoro-4-methoxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamide. Yield: 49.2%. ES-MS: m/e 321.0 (m+1).

1. customCollect the organic phase
2. dry with materialdry (K2CO3)
3. customevaporate
4. stirringKF (aqueous, 15%) (50 mL) and stir
5. temperatureat reflux for 1 h
6. additionPour the cooled solution over diatomaceous earth
7. filtrationfilter with MTBE (100 mL)
8. customCollect the organic phase
9. dry with materialdry (K2CO3)
10. customevaporate
11. washChromatography over silica gel, eluting with 10-30% THF in hexane