Ethyl nitroacetate → 3-(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-2-nitro-propionic Acid Ethyl Ester

HRID 11697

Reaction equation

HRID 11697 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[CH2:5][N+:6]([O-:8])=[O:7])[CH3:2].C(=O)(O)[O-].[Na+].[Cl:15][C:16]1[CH:41]=[CH:40][C:19]([O:20][CH2:21][C:22]([N:24]2[CH2:29][C@H:28]([CH3:30])[N:27]([CH2:31][C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[CH2:26][C@H:25]2[CH3:39])=[O:23])=[C:18]([CH2:42]Cl)[CH:17]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:1]([O:3][C:4](=[O:9])[CH:5]([N+:6]([O-:8])=[O:7])[CH2:42][C:18]1[CH:17]=[C:16]([Cl:15])[CH:41]=[CH:40][C:19]=1[O:20][CH2:21][C:22]([N:24]1[CH2:29][C@H:28]([CH3:30])[N:27]([CH2:31][C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[CH2:26][C@H:25]1[CH3:39])=[O:23])[CH3:2]

Participants

6

Reactant 3

HCID 69379Ethyl nitroacetateHCID 516892Sodium BicarbonateHCID 234058422-[4-Chloro-2-(chloromethyl)phenoxy]-1-{(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl}ethan-1-one

Product 1

HCID 865911673-(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-2-nitro-propionic Acid Ethyl EsterYield 47%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To nitro-acetic acid ethyl ester (0.32 g, 2.39 mmol), sodium bicarbonate (0.10 g, 1.19 mmol) and tetrabutyl ammonium iodide (0.088 g, 0.24 mmol) in dimethyl formamide (5 ml) was added 2-(4-chloro-2-chloromethyl-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.52 g, 1.19 mmol). After 1 hour of heating at 60° C. the reaction was concentrated and then diluted with methylene chloride. After washing with aqueous saturated sodium bicarbonate and saturated sodium chloride the organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel gave the title compound (0.30 g).

Workup

  1. concentrationwas concentrated
  2. additiondiluted with methylene chloride
  3. washAfter washing with aqueous saturated sodium bicarbonate and saturated sodium chloride the organic layer
  4. dry with materialwas dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-34e48198b45f4c59b72297ec362acb71
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Linked notes

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