Cyclohexylisopropylamine → 3-(2,4-Dichloro-pyrimidin-5-yl)-2-pyridin-3-yl-propionic acid ethyl ester

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

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 10 minutes, a solution of 2-pyridin-3-yl-acetic acid ethyl ester (1.65 g, 10.0 mmol) (Acros) in tetrahydrofuran (5 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 10 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 2 hours then slowly allowed to warm up to −20° 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-pyridin-3-yl-propionic acid ethyl ester as a brown oil. (Yield 1.10 g, 68.0%).

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