Sodium hydride → 2-(5-Chloro-3-Nitro-Pyridin-2-Yloxy)-1-[4-(4-Fluoro-Benzyl)-(2R,5S)-2,5-Dimethyl-Piperazin-1-Yl]Ethanone

HRID 11716Notes

Reaction equation

HRID 11716 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][N:7]2[C@@H:12]([CH3:13])[CH2:11][N:10]([C:14](=[O:17])[CH2:15][OH:16])[C@H:9]([CH3:18])[CH2:8]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:24]1[C:29]([N+:30]([O-:32])=[O:31])=[CH:28][C:27]([Cl:33])=[CH:26][N:25]=1>C1(C)C=CC=CC=1>[Cl:33][C:27]1[CH:28]=[C:29]([N+:30]([O-:32])=[O:31])[C:24]([O:16][CH2:15][C:14]([N:10]2[CH2:11][C@H:12]([CH3:13])[N:7]([CH2:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:20][CH:19]=3)[CH2:8][C@H:9]2[CH3:18])=[O:17])=[N:25][CH:26]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 80633312,5-Dichloro-3-nitropyridineHCID 234058381-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-hydroxy-ethanone

Product 1

HCID 696556572-(5-Chloro-3-Nitro-Pyridin-2-Yloxy)-1-[4-(4-Fluoro-Benzyl)-(2R,5S)-2,5-Dimethyl-Piperazin-1-Yl]EthanoneYield 89.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-hydroxy-ethanone (0.90 g, 3.2 mmol) in toluene (20 mL) at 0° C. was added sodium hydride (0.18 g, 4.5 mmol, 60% dispersion in mineral oil). The reaction was stirred for 15 minutes, then 2,5-dichloro-3-nitro-pyridine (0.65 g, 3.38 mmol) was added and the solution was stirred at ambient temperature for 18 hours. The reaction was quenched by the slow addition of water (5 mL) then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography on silica gel gave the title compound (1.25 g).

Workup

  1. stirringthe solution was stirred at ambient temperature for 18 hours
  2. customThe reaction was quenched by the slow addition of water (5 mL)
  3. extractionthen extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a0344112e3c4eae845fa2698f0127bd
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Reaction notes

Loading…