Ethyl 2-pyridinecarboxylate → 1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-3-(pyridin-2-yl)propane-1,3-dione

HRID 1913486Notes

Reaction equation

HRID 1913486 reaction equation
[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C:11](=[O:13])[CH3:12])[CH:9]=[CH:10][C:2]1=2.[H-].[Na+].[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](OCC)=[O:23]>C1COCC1>[O:1]1[CH2:6][CH2:5][O:4][C:3]2[CH:7]=[C:8]([C:11](=[O:13])[CH2:12][C:22]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][N:16]=3)=[O:23])[CH:9]=[CH:10][C:2]1=2

Participants

5

Reactant 3

HCID 17307Ethyl 2-pyridinecarboxylateHCID 24758Sodium hydrideHCID 761431,4-Benzodioxan-6-yl methyl ketone

Product 1

HCID 568403841-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-3-(pyridin-2-yl)propane-1,3-dioneYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethanone (XV) (1 eq) in THF was added slowly to a suspension of NaH (1.5 eq) in THF stirred under nitrogen at room temperature. The solution was further allowed to stir at room temperature until the evolution of gas was ceased. Ethyl picolinate (XIX) (1.1 eq) was added to the solution and refluxed overnight under nitrogen. The solution was cooled, poured into ice water and extracted with ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated under vacuum. The crude product was purified by column chromatography over silica gel to produce 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(pyridin-2-yl)propane-1,3-dione 15 as a yellow solid (71% yield), 1H NMR (CDCl3, 400 MHz): δ ppm 4.13-4.43 (m, 4H), 6.94 (d, J=8.31 Hz, 1H), 7.42 (m, 1H), 7.44 (m, 1H) 7.59 (m, 2H), 7.85 (m, 1H), 8.14 (d, J=7.81, 1H), 8.65 (m, 1H); ESIMS found C16H13NO4 m/z 284 (M+H).

Workup

  1. stirringto stir at room temperature until the evolution of gas
  2. temperaturerefluxed overnight under nitrogen
  3. temperatureThe solution was cooled
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe crude product was purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-e8711200dcac40fb83074b6114e73e66
Source dataset
uspto-grants-2013_12
Patent number
US08609717B2

Reaction notes

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