Reaktion #11885

Reaktionsgleichung

2,4-dichloro-5-iodomethyl-pyrimidine

2,4-Dichloro-5-(iodomethyl)pyrimidine

3,4-dimethoxyphenylacetic acid ethyl ester

N-isopropylcyclohexylamine

n-butyllithium

→

3-(2,4-dichloro-pyrimidin-5-yl)-2-(3,4-dimethoxy-phenyl)-propionic acid ethyl ester

Lösungsmittel

ethyl acetate

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture was stirred at the same temperature for 1 hour
2. 2
   Temperaturto warm up to −30° C.
3. 3
   workup.STIRRINGstirred for 10 minutes
4. 4
   TemperaturAfter cooling the reaction mixture
5. 5
   Waschensuccessively washed with saturated aqueous ammonium chloride solution (50 mL), water (30 mL) and brine (30 mL)
6. 6
   Trocknendried over anhydrous sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated in vacuo
9. 9
   SonstigeThe residue was then purified by flash column chromatography

Vorschrift

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 3,4-dimethoxyphenylacetic acid ethyl ester (1.12 g, 5.0 mmol) (Lancaster) 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 the 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. After cooling 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 then purified by flash column chromatography to give 3-(2,4-dichloro-pyrimidin-5-yl)-2-(3,4-dimethoxy-phenyl)-propionic acid ethyl ester. (Yield 440 mg, 46.0%).

Quelle