Pyridine → HCID 56652980, compound

HRID 2410209Notes

Reaction equation

HRID 2410209 reaction equation
C(C1C(O)=C(C=C(/C=C/C(=O)C2C=C(OC)[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=2)C=1)C=O)(C)(C)C.[CH:30]([C:34]1C(O)=[C:36]([CH:39]=[C:40](/[CH:42]=[CH:43]/[C:44](=[O:52])[C:45]2[CH:50]=[CH:49]C(C)=CC=2)[CH:41]=1)[CH:37]=O)([CH2:32][CH3:33])[CH3:31].[C:54]([O:61][CH3:62])(=[O:60])[CH2:55][C:56]([O:58][CH3:59])=[O:57].N1C=CC=C[CH:64]=1.C1C[O:72][CH2:71]C1>>[CH:30]([C:34]1[CH:41]=[C:40](/[CH:42]=[CH:43]/[C:44](=[O:52])[C:45]2[CH:17]=[C:18]([O:26][CH3:27])[C:19]([O:24][CH3:25])=[C:49]([O:72][CH3:71])[CH:50]=2)[CH:39]=[C:36]2[C:59]=1[O:58][C:56](=[O:57])[C:55]([C:54]([O:61][CH2:62][CH3:64])=[O:60])=[CH:37]2)([CH2:32][CH3:33])[CH3:31]

Participants

6

Reactant 5

HCID 1049PyridineHCID 7943Dimethyl malonateHCID 8028TetrahydrofuranHCID 56653336HCID 56653336, compoundHCID 56653338HCID 56653338, compound

Product 1

HCID 56652980HCID 56652980, compound

Procedure

A solution of (E)-3-tert-butyl-2-hydroxy-5-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-enyl)benzaldehyde of formula III (0.5 g, 1.26 mmol), dimethyl malonate (0.20 g, 1.26 mmol) in THF (20 mL) was treated with pyridine (0.4 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 (40 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 (E)-methyl 8-tert-butyl-2-oxo-6-(3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-enyl)-2H-chromene-3-carboxylate (General Formula IV). (0.48 g, 79% yield). White solid, m. p. 145-146° C.; 1H NMR (CDCl3 300 MHz): δ 8.57 (s, 1H), 7.86 (d, J=1.7 Hz, 1H), 7.84-7.78 (m, 1H) 7.74 (d, J=1.6 Hz, 1H), 7.47 (d, J=15.6 Hz, 1H), 7.28 (s, 2H), 3.96 (brs, 12H), 1.55 (s, 9H); 13C NMR (CDCl3, 75 MHz): δ 188.8, 163.6, 155.7, 155.1, 153.3, 149.5, 143.0, 142.8, 139.1, 133.3, 131.8, 131.3, 127.4, 122.7, 118.8, 118.0, 106.4, 61.1, 56.6, 53.0, 35.0, 29.7; ESI-MS (m/z): 481 (M+H)+.

Workup

  1. temperaturerefluxed
  2. customMost of the excess solvent was evaporated under reduced pressure
  3. additionTo this residue water (40 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-5ce9232349f546a8859be8dfbf597e9a
Source dataset
uspto-grants-2014_08
Patent number
US08815940B2

Reaction notes

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