Реакция #56832

Уравнение реакции

(5-chloro-2-methoxy-phenyl)-imidazol-1-yl-methanone

hydrochloric acid

ethyl malonate sodium salt

magnesium sulfate

magnesium chloride

triethylamine

→

3-(5-chloro-2-methoxy-phenyl)-3-oxopropionic acid ethyl ester

Выход 76.0%

Растворители

acetonitrile

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGAfter stirring at 80° C. for 2 hours
3. 3
   workup.STIRRINGthe mixture was stirred for 16 hours
4. 4
   workup.STIRRINGthe mixture was stirred for 30 minutes
5. 5
   ДругоеThe layers were separated
6. 6
   Экстракцияthe aqueous layer was extracted with ethyl acetate (3×60 ml)
7. 7
   СушкаThe combined organic layers were dried over magnesium sulfate
8. 8
   Концентрированиеconcentrated under reduced pressure
9. 9
   ДругоеThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:4 followed by 1:3)

Методика

To a stirred mixture of ethyl malonate sodium salt (3.8 g, 24.7 mmol) and magnesium sulfate (3.2 g, 26.3 mmol) in acetonitrile (60 ml) was added triethylamine (4.7 ml, 33.5 mmol) under an argon atmosphere. After stirring for 2 hours, the solution containing (5-chloro-2-methoxy-phenyl)-imidazol-1-yl-methanone was added. After stirring at 80° C. for 2 hours, magnesium chloride (2.5 g, 26.3 mmol) was added and the mixture was stirred for 16 hours. After cooling to 10° C., concentrated hydrochloric acid (5 ml) was added and the mixture was stirred for 30 minutes. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×60 ml). The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:4 followed by 1:3) to provide 3-(5-chloro-2-methoxy-phenyl)-3-oxopropionic acid ethyl ester (2.3 g, 76% yield) as an oil. 1H NMR (CDCl3) δ 1.23 (t, 3H, J=8.7 Hz CH3), 3.89 (s, 3H, CH3), 3.94 (s, 2H, CH2), 4.17 (q, 2H, CH2), 6.91 (d, 1H, J=8.6 Hz, Ar), 7.45 (dd, 1H, J=8.8 Hz, J=2.6 Hz, Ar), 7.85 (d, 1H, J=2.6 Hz, Ar).

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