反応 #11885

ord-6595dcbcaa4e4ea4ba99ea2f8bf33099

反応条件

温度
-78°CELSIUS
詳細条件
See reaction.notes.procedure_details.

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
    温度After cooling the reaction mixture
  5. 5
    洗浄successively washed with saturated aqueous ammonium chloride solution (50 mL), water (30 mL) and brine (30 mL)
  6. 6
    乾燥dried over anhydrous sodium sulfate
  7. 7
    ろ過filtered
  8. 8
    濃縮concentrated in vacuo
  9. 9
    その他The residue was then purified by flash column chromatography

実験手順

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%).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US07098332B2uspto-grants-2006_08