反応 #11868

反応方程式

2,4-dichloro-5-iodomethyl-pyrimidine

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

phenylacetic acid methyl ester

N-isopropylcyclohexylamine

n-butyllithium

→

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

溶媒

ethyl acetate

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   workup.STIRRINGthe reaction mixture was stirred at the same temperature for 1 hour
2. 2
   温度to warm up to −30° C.
3. 3
   workup.STIRRINGstirred for 10 minutes
4. 4
   洗浄successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL)
5. 5
   乾燥dried over anhydrous sodium sulfate
6. 6
   ろ過filtered
7. 7
   濃縮concentrated in vacuo
8. 8
   その他The residue was purified by flash column chromatography

実験手順

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 phenylacetic acid methyl ester (1.50 g, 10.0 mmol) (Aldrich) 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-phenyl-propionic acid methyl ester as a colorless oil. (Yield 1.00 g, 64.5%).

出典