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 11677ノート

反応式

HRID 11677 の反応式
[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

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f1f9202db30d424fb22cfc53749aed0e
出典データセット
uspto-grants-2006_08
特許番号
US07098212B2

反応ノート

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