Dimethyl malonate → HCID 75967836, compound

HRID 2410201Notes

Reaction equation

HRID 2410201 reaction equation
[CH:1]([C:5]1[C:6](O)=[C:7]([CH:10]=[C:11]([CH:13]=[CH:14][C:15]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[O:16])[CH:12]=1)C=O)([CH2:3][CH3:4])[CH3:2].C(C1C(O)=C(C=C(/C=C/C(=O)C2C=CC(C)=CC=2)C=1)C=O)(CC)C.[C:49]([O:56][CH3:57])(=[O:55])[CH2:50][C:51]([O:53][CH3:54])=[O:52].CN1CCOCC1>CO>[CH:1]([C:5]1[CH:12]=[C:11]([CH:13]=[CH:14][C:15]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)=[O:16])[CH:10]=[C:7]2[C:54]=1[O:53][C:51](=[O:52])[C:50]([C:49]([O:56][CH3:57])=[O:55])=[CH:6]2)([CH2:3][CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 7943Dimethyl malonateHCID 79724-MethylmorpholineHCID 56653338HCID 56653338, compoundHCID 86692171HCID 86692171, compound

Product 1

HCID 75967836HCID 75967836, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 3-sec-butyl-5-(3-(4-chlorophenyl)-3-oxoprop-1-enyl)-2-hydroxybenzaldehyde of formula III (0.5 g, 1.46 mmol), dimethyl malonate (0.19 g, 1.46 mmol) in methanol (30 mL) was treated with N-methyl morpholine (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 (25 mL) was added and extracted 3-fold with 25 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. Concentration provides methyl 8-sec-butyl-6-(3-(4-chlorophenyl)-3-oxoprop-1-enyl)-2-oxo-2H-chromene-3-carboxylate (General Formula IV). (0.49 g, 80% yield). White solid, m. p. 145-146° C.; 1H NMR (CDCl3, 300 MHz); δ 8.59 (s, 1H), 7.99 (d, 2H, J=8.5 Hz), 7.84-7.75 (m, 3H), 7.58-7.47 (m, 3H), 4.0 (s, 3H), 3.45-3.36 (m, 1H), 1.78-1.69 (m, 2H), 1.32 (d, 3H, J=7.0 Hz), 0.89 (t, 3H, J=7.3 Hz): 13C NMR (CDCl3, 75 MHz); δ 188.6, 163.4, 156.1, 154.0, 149.1, 143.1, 139.5, 136.7, 136.2, 131.6, 131.4, 130.0, 129.0, 127.3, 122.3, 118.4, 118.2, 52.9, 33.5, 29.6, 20.4. 12.0; ESI-MS (m/z): 425 (M+H)+.

Workup

  1. temperaturerefluxed
  2. customMost of the excess solvent was evaporated under reduced pressure
  3. additionTo this residue water (25 mL) was added
  4. extractionextracted 3-fold with 25 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
  10. concentrationConcentration

Sources & evidence

ORD record
ord-db72e3f13a594f13bf5cc085c2c9c85c
Source dataset
uspto-grants-2014_08
Patent number
US08815940B2

Reaction notes

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