Ethyl 4-methoxyphenylacetate → Ethyl 3-(4-cyano-2-methylphenyl)-2-(4-methoxyphenyl)-3-oxopropanoate

To a solution of (4-methoxy-phenyl)-acetic acid ethyl ester (25.96 g, 133.7 mmol) in anhydrous tetrahydrofuran (200 mL) was added lithium hexamethyldisilazide (200 mL, 1 M) at −78° C. under nitrogen. After being stirred for 15 min., a solution of A-5 (4-cyano-2-methylbenzoyl chloride) (24 g, 133.6 mmol) in anhydrous tetrahydrofuran (150 mL) was added dropwise, and the resulting mixture was stirred at room temperature overnight for 16 h. The reaction mixture was quenched by the addition of saturated aqueous ammonium chloride solution (200 mL), and the resultant mixture was extracted with ethyl acetate (100 mL×3). The combined organic layers were dried over anhydrous sodium sulfate (20 g), filtered, and evaporated. The residue was purified on silica gel column (petroleum ether/ethyl acetate=25:1) to give A-6 (ethyl 3-(4-cyano-2-methylphenyl)-2-(4-methoxyphenyl)-3-oxopropanoate) (40 g, yield 88.7%).

1. stirringthe resulting mixture was stirred at room temperature overnight for 16 h
2. customThe reaction mixture was quenched by the addition of saturated aqueous ammonium chloride solution (200 mL)
3. extractionthe resultant mixture was extracted with ethyl acetate (100 mL×3)
4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate (20 g)
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified on silica gel column (petroleum ether/ethyl acetate=25:1)

ORD record

ord-910c7e7fd2784b3083d30706730155d7

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029402B2