Реакция #11885

Уравнение реакции

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

Растворители

ethyl acetate

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Условия реакции

Обработка

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

Методика

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%).

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