Diethyl Malonate → HCID 52947305, compound

HRID 2410200Notes

Reaction equation

HRID 2410200 reaction equation
[CH:1]([C:5]1[C:6]([OH:15])=[C:7]([CH:13]=O)[CH:8]=[C:9]([CH:12]=1)[CH:10]=[O:11])([CH2:3][CH3:4])[CH3:2].[C:16](OCC)(=[O:23])[CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].N1CCCCC1>C(O)C>[CH:1]([C:5]1[CH:12]=[C:9]([CH:10]=[O:11])[CH:8]=[C:7]2[C:6]=1[O:15][C:16](=[O:23])[C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:13]2)([CH2:3][CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 8082PiperidineHCID 71545842HCID 71545842, compound

Product 1

HCID 52947305HCID 52947305, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 5-sec-butyl-4-hydroxyisophthalaldehyde of formula I (0.5 g, 2.42 mmol), diethyl malonate (0.38 g, 2.42 mmol) in ethanol (20 mL) was treated with piperidine (0.3 mL) and refluxed. Most of the excess solvent was evaporated under reduced pressure, and the residue was neutralized with acetic acid. To this residue water (20 mL) was added and extracted 3-fold with 20 mL of CHCl3. The combined organic layers were dried on Na2SO4, filtered, and concentrated to dryness under reduced pressure. The residue was chromatographed over silica gel (SiO2, 230-400 flash), eluting with a gradient of 20% ethyl acetate in hexane to 40% ethyl acetate in hexane, which upon concentration provides ethyl 8-sec-butyl-6-formyl-2-oxo-2H-chromene-3-carboxylate (General Formula II). (0.47 g, 65% yield). White solid, m. p. 89-90° C.; 1H NMR (CDCl3, 300 MHz): δ 10.05 (s, 1H), 8.60 (s, 1H), 8.05 (brs, 1H), 8.01 (brs, 1H) 4.44 (q, 2H, J=7.1 Hz), 3.51-3.40 (m, 1H), 1.78-1.69 (m, 2H), 1.43 (t, 3H, J=7.1 Hz), 1.33 (d, 3H, J=7 Hz), 0.88 (t, 3H, J=7.4 Hz); 13C NMR (CDCl3, 75 MHz): δ 190.2, 162.7, 156.5, 155.8, 148.5, 137.3, 132.9, 131.7, 129.9, 119.2, 118.0, 62.2, 33.4, 29.6, 20.4, 14.2, 12.0; ESI-MS (m/z): 303 (M+H)+.

Workup

  1. temperaturerefluxed
  2. customMost of the excess solvent was evaporated under reduced pressure
  3. additionTo this residue water (20 mL) was added
  4. extractionextracted 3-fold with 20 mL of CHCl3
  5. customThe combined organic layers were dried on Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe residue was chromatographed over silica gel (SiO2, 230-400 flash)
  9. washeluting with a gradient of 20% ethyl acetate in hexane to 40% ethyl acetate in hexane, which upon concentration

Sources & evidence

ORD record
ord-bc491405b4c14b9da2c6e8a6406afa2c
Source dataset
uspto-grants-2014_08
Patent number
US08815940B2

Reaction notes

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