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

Participants

Reaction Conditions

Reaction Steps

To a solution of N-isopropylcyclohexylamine (720 mg, 5.0 mmol) (Aldrich) in dry tetrahydrofuran (10 mL) was added n-butyllithium (2.5 M in hexanes, 2.0 mL, 5.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 4-methoxyphenylacetic acid methyl ester (900 mg, 5.0 mmol) (Aldrich) in tetrahydrofuran (3 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 30 minutes. To this reaction mixture was added a solution of 2,4-dichloro-5-iodomethyl-pyrimidine (722. 5 mg, 2.5 mmol) (from Example 1c supra) in tetrahydrofuran (3 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 (50 mL), water (30 mL), and brine (30 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-(4-methoxy-phenyl)-propionic acid methyl ester as a yellow oil. (Yield 620 mg, 72.7%).

Provenance & Evidence