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 11677Notes

Reaction equation

HRID 11677 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-f1f9202db30d424fb22cfc53749aed0e
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Reaction notes

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