تفاعل #11885

معادلة التفاعل

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

المذيبات

ethyl acetate

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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%).

المصدر