反应详情

Ethyl chloroacetate (8.0 mL, 1.3 eq.) was added to a mixture of 2-chloro-6-hydroxy-benzaldehyde (Example 1a), 9.0 g, 57 mmol) and potassium carbonate (16.0 g, 114 mmol) in DMF (100 mL) at rt. The reaction mixture was heated at +120° C. for 1.5 h, cooled to room temperature and filtered through a short bed of Celite. The filtrate was acidified to pH 2 with 5 M HCl and the solution was extracted with dichloromethane (2×100 mL). The combined organic extracts was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography by using hexane/ethyl acetate (9/1) as eluent to give the title compound. Yield: 10 g (77%). 1H NMR (400 MHz, CDCl3) δ ppm 1.44 (t, 3H) 4.56 (q, 2H) 7.29-7.32 (m, 1H) 7.35-7.40 (m, 1H) 7.49-7.52 (m, 1H) 7.60 (s, 1H).

1. temperatureThe reaction mixture was heated at +120° C. for 1.5 h
2. filtrationfiltered through a short bed of Celite
3. extractionthe solution was extracted with dichloromethane (2×100 mL)
4. washThe combined organic extracts was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude residue was purified by silica gel column chromatography