p-Nitroacetophenone → 1-(2-Methoxy pyridine-3-yl)-3-(4-nitrophenyl)propane-1,3-dione

HRID 884731Notes

Reaction equation

HRID 884731 reaction equation
[CH3:1][O:2][C:3]1[N:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=O.CN1CCOCC1.C(OC(Cl)=O)C.[N+:25]([C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][CH:29]=1)([O-:27])=[O:26].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH4+].[Cl-]>C1COCC1.C(OCC)(=O)C.O>[CH3:1][O:2][C:3]1[C:4]([C:5](=[O:7])[CH2:35][C:34]([C:31]2[CH:30]=[CH:29][C:28]([N+:25]([O-:27])=[O:26])=[CH:33][CH:32]=2)=[O:36])=[CH:8][CH:9]=[CH:10][N:11]=1

Participants

10

Reactant 6

HCID 7487p-NitroacetophenoneHCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 7080932-Methoxynicotinic acidHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 666501871-(2-Methoxy pyridine-3-yl)-3-(4-nitrophenyl)propane-1,3-dioneYield 62%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

To a stirred solution of 2-methoxynicotinic acid (2.3 g, 15 mmol) in 75 mL anhydrous THF was added N-methyl morpholine (1.52 g, 15 mmol). The reaction mixture was cooled to −10° C. Ethylchloroformate (1.63 g, 15 mmol) was added dropwise at −10° C. The reaction mixture was stirred at −10° C. for 15 min. and then at rt for 10 h. Water (50 mL) was added, and the solution was extracted with ethyl acetate. The organic layer was separated, dried (Na2SO4), and concentrated to give a colorless liquid in 97% yield (3.29 g). To a solution of this colorless liquid (3.28 g, 14.57 mmol) and 4′-nitroacetophenone (2.477 g, 15 mmol) in anhydrous THF (75 mL) was added lithium bis(trimethylsilyl)amide 1.0M solution in THF (18 mL) at −30° C. over a period of 45 min. Stirring continued at −30° C. for 30 min. The reaction mixture was allowed to warm to rt. The stirring was continued for another 15 h at rt, and the reaction mixture was then diluted with ethyl acetate (200 mL). Saturated NH4Cl solution (50 mL) was added. The organic layer was separated and dried over anhydrous Na2SO4. Removal of solvent gave the crude product which was triturated with ether to give 1-(2-methoxy pyridine-3-yl)-3-(4-nitrophenyl)propane-1,3-dione as yellow solid in 62% yield (2.79 g).

Workup

  1. waitat rt for 10 h
  2. extractionthe solution was extracted with ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customto give a colorless liquid in 97% yield (3.29 g)
  7. stirringStirring
  8. waitcontinued at −30° C. for 30 min
  9. temperatureto warm to rt
  10. waitThe stirring was continued for another 15 h at rt
  11. customThe organic layer was separated
  12. dry with materialdried over anhydrous Na2SO4
  13. customRemoval of solvent
  14. customgave the crude product which
  15. customwas triturated with ether

Sources & evidence

ORD record
ord-c343e9786878405a98310abf0846e157
Source dataset
uspto-grants-2012_08
Patent number
US08242130B2

Reaction notes

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