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Cyclohexylisopropylamine → 3-(2,4-Dichloro-pyrimidin-5-yl)-2-(3,5-dimethoxy-phenyl)-propionic acid methyl ester

HRID 11769
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HRID 11769 반응식
C(NC1CCCCC1)(C)C.C([Li])CCC.[CH3:16][O:17][C:18](=[O:30])[CH2:19][C:20]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[CH:21]=1.[Cl:31][C:32]1[N:37]=[C:36]([Cl:38])[C:35]([CH2:39]I)=[CH:34][N:33]=1>O1CCCC1.C(OCC)(=O)C>[CH3:16][O:17][C:18](=[O:30])[CH:19]([C:20]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[C:22]([O:28][CH3:29])[CH:21]=1)[CH2:39][C:35]1[C:36]([Cl:38])=[N:37][C:32]([Cl:31])=[N:33][CH:34]=1
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참가 물질

7

반응물 4

HCID 62386CyclohexylisopropylamineHCID 592191Methyl 3,5-dimethoxyphenylacetateHCID 219393522,4-Dichloro-5-(iodomethyl)pyrimidineHCID 178418339Butyllithium

생성물 1

HCID 210443203-(2,4-Dichloro-pyrimidin-5-yl)-2-(3,5-dimethoxy-phenyl)-propionic acid methyl ester

시약·촉매·용매 2

HCID 8028
Tetrahydrofuran
용매
3회
HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

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 3,5-dimethoxy-phenyl-acetic acid methyl ester (2.05 g, 9.76 mmol) (from Example 3a supra) 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 this 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-(3,5-dimethoxy-phenyl)-propionic acid methyl ester as a colorless oil. (Yield 1.45 g, 78.0%).

후처리

  1. stirringthe reaction mixture was stirred at the same temperature for 1 hour
  2. temperatureto warm up to −30° C.
  3. stirringstirred for 10 minutes
  4. washsuccessively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-ccebbc825e74486f8f8653f180c27aab
출처 데이터셋
uspto-grants-2006_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07098332B2

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