反应详情

Diethyl acetylsuccinate (2.4 g, 11.1 mmol) is added to a solution of Compound 4 (1.3 g, 8.9 mmol) in 20 mL methanesulfonic acid at 20° C. The reaction is stirred for 16 hours and poured into 200 mL ice water. The product is extracted with EtOAc (80 mL×2), washed with brine (40 mL), dried over anhydrous MgSO4, and concentrated in vacuo to yield a brown oil. The crude oil is purified by column chromatography on silica gel eluted with CHCl3 /MeOH (95:5 to 90:10) to yield 1.06 g (40%) of Compound 10 as an off-white solid. 1H-NMR (DMSO-d6) δ 7.56 (d, 1H), 4.08 (q, 2H), 3.67 (s, 2H), 2.34 (s, 3H), 1.19 (t, 3H). 19F-NMR (DMSO-d6) Φ 130.13 (t, 1F), 148.87 (d, 1F). Also isolated from the column is 0.50 g (20%) of 6,8-difluoro-7-hydroxy-4-methylcoumarin 3-acetic acid (Compound 11).

1. extractionThe product is extracted with EtOAc (80 mL×2)
2. washwashed with brine (40 mL)
3. dry with materialdried over anhydrous MgSO4
4. concentrationconcentrated in vacuo
5. customto yield a brown oil
6. customThe crude oil is purified by column chromatography on silica gel
7. washeluted with CHCl3 /MeOH (95:5 to 90:10)