Dimethyl malonate → HCID 18959456, compound

HRID 1708537Notes

Reaction equation

HRID 1708537 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[C:5]([Cl:23])=[CH:4][C:3]=1[N+:24]([O-:26])=[O:25].[C:27]([O:34][CH3:35])(=[O:33])[CH2:28][C:29]([O:31][CH3:32])=[O:30].[H-].[Na+].[Cl-].[NH4+]>CN1CCCC1=O>[Cl:23][C:5]1[C:6]([CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[CH:7][C:2]([CH:28]([C:27]([O:34][CH3:35])=[O:33])[C:29]([O:31][CH3:32])=[O:30])=[C:3]([N+:24]([O-:26])=[O:25])[CH:4]=1

Participants

6

Reactant 4

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 18959455HCID 18959455, compound

Product 1

HCID 18959456HCID 18959456, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
57 °C

Procedure

2,5-Dichloro-4-(2-[4-(t-butoxycarbonyl)-1-piperazinyl]ethyl)-nitrobenzene (5 g, 13 mmol) and dimethyl malonate (3.8 ml, 33 mmol) were stirred in N-methyl pyrrolidone (75 ml), at room temperature under nitrogen, while sodium hydride (1.33 g, 33 mmol, 60% in oil) was added. The reaction mixture was heated to 57° C. for 7 hours. The reaction mixture was cooled and poured into saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The combined organic layers were washed with water three times, one time with brine and dried over magnesium sulfate. Evaporation of the solvent in vacuo gave an oil which was chromatographed over flash silica gel with ethyl acetate/hexanes followed by ethyl acetate. The fractions containing the desired product were combined and evaporated to give an oil, 2.5 g, 48% yield. NMR (CDCl3) δ 8.09 (s, 1), 7.45 (s, 1), 5.31 (s, 1), 3.79 (s, 6), 3.43 (m, 4), 2.98 (t, 2), 2.61 (t, 2), 2.47 (m, 4), 1.43 (s, 9).

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted twice with ethyl acetate
  4. washThe combined organic layers were washed with water three times, one time with brine
  5. dry with materialdried over magnesium sulfate
  6. customEvaporation of the solvent in vacuo
  7. customgave an oil which
  8. customwas chromatographed over flash silica gel with ethyl acetate/hexanes
  9. additionThe fractions containing the desired product
  10. customevaporated
  11. customto give an oil, 2.5 g, 48% yield

Sources & evidence

ORD record
ord-af5e83d173f3414387ed51cd5944be6b
Source dataset
uspto-grants-1994_10
Patent number
US05359068

Reaction notes

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