Reaktion #11868

ord-3047c52f326d4823ad745add3224ef15

Reaktionsgleichung

Clc1ncc(CI)c(Cl)n1
2,4-dichloro-5-iodomethyl-pyrimidine
Clc1ncc(CI)c(Cl)n1
2,4-Dichloro-5-(iodomethyl)pyrimidine
COC(=O)Cc1ccccc1
phenylacetic acid methyl ester
CC(C)NC1CCCCC1
N-isopropylcyclohexylamine
[Li][CH2]CCC
n-butyllithium
COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1
3-(2,4-dichloro-pyrimidin-5-yl)-2-phenyl-propionic acid methyl ester

Reaktionsbedingungen

Temperatur
-78°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

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
    Waschensuccessively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL)
  5. 5
    Trocknendried over anhydrous sodium sulfate
  6. 6
    Filtrationfiltered
  7. 7
    Einengenconcentrated in vacuo
  8. 8
    SonstigeThe residue was purified by flash column chromatography

Vorschrift

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%).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07098332B2uspto-grants-2006_08