反应详情

Ethyl acetoacetate (51.25 g, 390 mmol) was added dropwise to the stirred suspension of anhydrous magnesium chloride (37.54 g, 390 mmol) in dried dichloromethane (200 ml) over a period of 1 hour under argon atmosphere at 0° C. followed by pyridine (62.5 g, 788 mmol). After 15 minutes, 4-chlorobenzoylchloride (68.95 g, 394 mmol) was added dropwise and stirring was continued for 15 minutes at 0° C. and further stirred for 1.5 hours at 30° C. The resulting reaction mixture was neutralized with hydrochloric acid (6N, 235 ml) at 0-5° C., filtered and washed with water. The filtrate was extracted with diethylether (3×100 ml). The ether extract was washed with water, dried over anhydrous sodium sulphate and concentrated to dryness in vacuum. The obtained oil was taken in ammonium chloride (21 g in 200 ml water) solution containing ammonia (2 ml) and stirred at 30° C. for 20 minutes. The resulting solution was extracted with ethyl acetate (3×200 ml). Ethyl acetate extract was dried over anhydrous sodium sulphate, concentrated to yield the crude product, which was purified by column chromatography to yield the title compound as viscous oil (43 g, 48.2%). 1H-NMR (DMSO-d6): δ 1.15-1.18 (t, 3H), 4.08-4.13 (q, 2H), 4.20 (s, 2H), 7.61-7.64 (d, 2H), 7.94-7.97 (d, 2H). MS m/z: 227.1 (M+).

1. waitwas continued for 15 minutes at 0° C.
2. stirringfurther stirred for 1.5 hours at 30° C
3. customThe resulting reaction mixture
4. filtrationfiltered
5. washwashed with water
6. extractionThe filtrate was extracted with diethylether (3×100 ml)
7. extractionThe ether extract
8. washwas washed with water
9. dry with materialdried over anhydrous sodium sulphate
10. concentrationconcentrated to dryness in vacuum
11. additioncontaining ammonia (2 ml)
12. stirringstirred at 30° C. for 20 minutes
13. extractionThe resulting solution was extracted with ethyl acetate (3×200 ml)
14. extractionEthyl acetate extract
15. dry with materialwas dried over anhydrous sodium sulphate
16. concentrationconcentrated
17. customto yield the crude product, which
18. customwas purified by column chromatography