Hydrochloric Acid → Ethyl 3-(5-chloro-2-methoxyphenyl)-3-oxopropanoate

Temperature

10 °C

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).

1. additionwas added
2. stirringAfter stirring at 80° C. for 2 hours
3. stirringthe mixture was stirred for 16 hours
4. stirringthe mixture was stirred for 30 minutes
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate (3×60 ml)
7. dry with materialThe combined organic layers were dried over magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate-hexane (1:4 followed by 1:3)

ORD record

ord-bdb4a6607416413d9cebb779de9ff903

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419984B2