Diethyl Malonate → HCID 56652980, compound

HRID 2410208Notes

Reaction equation

HRID 2410208 reaction equation
C(C1[C:6](O)=[C:7]([CH:10]=[C:11](/[CH:13]=[CH:14]/[C:15](=[O:28])[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=2)[CH:12]=1)C=O)(CC)C.[CH:30](C1C(O)=C(C=C(/C=C/C(=O)C2C=CC(C)=CC=2)C=1)C=O)([CH2:32][CH3:33])[CH3:31].[C:54]([O:62][CH2:63][CH3:64])(=[O:61])[CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57].N1CCCCC1>C(O)C>[CH:30]([C:64]1[CH:12]=[C:11](/[CH:13]=[CH:14]/[C:15](=[O:28])[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=2)[CH:10]=[C:7]2[C:63]=1[O:62][C:54](=[O:61])[C:55]([C:56]([O:58][CH2:59][CH3:60])=[O:57])=[CH:6]2)([CH2:32][CH3:33])[CH3:31]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 8082PiperidineHCID 56653338HCID 56653338, compoundHCID 86692175HCID 86692175, compound

Product 1

HCID 56652980HCID 56652980, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (E)-3-sec-butyl-2-hydroxy-5-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-enyl)benzaldehyde of formula III (0.5 g, 1.26 mmol), diethyl malonate (0.20 g, 1.26 mmol) in ethanol (30 mL) was treated with piperidine (0.2 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 (35 mL) was added and extracted 3-fold with 15 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 (E)-ethyl 8-sec-butyl-2-oxo-6-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-enyl)-2 H-chromene-3-carboxylate (General Formula IV). (0.49 g, 78% yield). White solid, m. p. 128-129° C.; 1H NMR (CDCl3 300 MHz): δ 8.56 (s, 1H), 7.83-7.75 (m, 3H), 7.49 (d, J=15.6 Hz, 1H), 7.31-7.29 (m, 2H), 4.42 (q, J=7.1 Hz, 2H), 3.95 (brs, 9H), 3.45-3.36 (m, 1H), 1.78-1.69 (m, 2H), 1.42 (t, J=7.1 Hz, 3H) 3.33 (d, J=6.9 Hz, 3H) 0.89 (t, J=7.3 Hz, 3H); 13C NMR (CDCl3, 75 MHz): δ 188.8, 162.9, 156.3, 153.9, 153.3, 148.6, 142.9, 142.7, 136.7, 133.2, 131.8, 131.6, 126.8, 122.7, 118.8, 118.2, 106.4, 62.1, 61.1, 56.6, 50.8, 33.6, 29.7, 20.5, 14.3, 12.1; ESI-MS (m/z): 495 (M+H)+.

Workup

  1. temperaturerefluxed
  2. customMost of the excess solvent was evaporated under reduced pressure
  3. additionTo this residue water (35 mL) was added
  4. extractionextracted 3-fold with 15 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-8f164733f10a4e4a99b32bb74fb6a65d
Source dataset
uspto-grants-2014_08
Patent number
US08815940B2

Reaction notes

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