Cyclohexylisopropylamine → 3-(2,4-Dichloro-pyrimidin-5-yl)-2-(2-methoxy-phenyl)-propionic acid methyl ester

Temperatur

-78 °C

To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2-methoxyphenylacetic acid methyl ester (1.8 g, 10.0 mmol) (TCI-US) in tetrahydrofuran (5 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 30 minutes. To the reaction mixture was added a solution of 2,4-dichloro-5-iodomethyl-pyrimidine (1.45 g, 5.0 mmol) (from Example 1c supra) in tetrahydrofuran (5 mL) at −78° C. and the reaction mixture was stirred at the same temperature for 1 hour then slowly allowed to warm up to −30° C. and stirred for 10 minutes. The reaction mixture was diluted with ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to give 3-(2,4-dichloro-pyrimidin-5-yl)-2-(2-methoxy-phenyl)-propionic acid methyl ester as a yellow oil. (Yield 1.40 g, 82.3%).

1. stirringthe reaction mixture was stirred at the same temperature for 1 hour
2. temperatureto warm up to −30° C.
3. stirringstirred for 10 minutes
4. washsuccessively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash column chromatography

ORD-Eintrag

ord-aa434642a69645fba495e3907de3e968

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07098332B2