Sodium hydride → (5-Chloro-2-{2-[4-(4-Fluoro-Benzyl)-(2R,5S)-2,5-Dimethyl-Piperazin-1-Yl]-2-Oxo-Ethoxy}-Pyridin-3-Yl)-Acetic Acid Methyl Ester

HRID 11677노트

반응식

HRID 11677 반응식
[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[C:6](Cl)=[N:7][CH:8]=[C:9]([Cl:11])[CH:10]=1.[F:14][C:15]1[CH:33]=[CH:32][C:18]([CH2:19][N:20]2[C@@H:25]([CH3:26])[CH2:24][N:23]([C:27](=[O:30])[CH2:28][OH:29])[C@H:22]([CH3:31])[CH2:21]2)=[CH:17][CH:16]=1.[H-].[Na+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[C:6]([O:29][CH2:28][C:27]([N:23]2[CH2:24][C@H:25]([CH3:26])[N:20]([CH2:19][C:18]3[CH:17]=[CH:16][C:15]([F:14])=[CH:33][CH:32]=3)[CH2:21][C@H:22]2[CH3:31])=[O:30])=[N:7][CH:8]=[C:9]([Cl:11])[CH:10]=1.[Cl:11][C:9]1[CH:10]=[C:5]([CH2:4][C:3]([OH:2])=[O:13])[C:6]([O:29][CH2:28][C:27]([N:23]2[CH2:24][C@H:25]([CH3:26])[N:20]([CH2:19][C:18]3[CH:17]=[CH:16][C:15]([F:14])=[CH:33][CH:32]=3)[CH2:21][C@H:22]2[CH3:31])=[O:30])=[N:7][CH:8]=1

참가 물질

6

반응물 3

HCID 24758Sodium hydrideHCID 234058381-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-hydroxy-ethanoneHCID 85826719(2,5-Dichloro-pyridin-3-yl)-acetic Acid Methyl Ester

생성물 2

HCID 69655283(5-Chloro-2-{2-[4-(4-Fluoro-Benzyl)-(2R,5S)-2,5-Dimethyl-Piperazin-1-Yl]-2-Oxo-Ethoxy}-Pyridin-3-Yl)-Acetic Acid Methyl EsterHCID 69655717(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-yl)-acetic acid

시약·촉매·용매 1

HCID 1140Toluene용매2회

실험 절차

To a 0° C. solution of (2,5-dichloro-pyridin-3-yl)-acetic acid methyl ester (0.45 g, 2.05 mmol) and 1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-hydroxy-ethanone (0.52 g, 1.86 mmol) in toluene (5.5 mL) was added sodium hydride (0.082 g, 2.05 mmol, 60% dispersion in mineral oil) in toluene (9.3 mL). The reaction mixture was slowly warmed to ambient temperature and then heated to reflux overnight. The resulting reaction mixture was cooled to ambient temperature, quenched with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel gave the title compound (0.14 g) and (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-pyridin-3-yl)-acetic acid (0.20 g).

후처리

  1. temperatureheated
  2. temperatureto reflux overnight
  3. customThe resulting reaction mixture
  4. temperaturewas cooled to ambient temperature
  5. customquenched with water
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-f1f9202db30d424fb22cfc53749aed0e
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07098212B2

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