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

Temperature

-78 °C

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%).

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 (50 mL), water (30 mL), and brine (30 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 record

ord-1f20269900804e01908b99c9d221b00d

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07098332B2