Pyridine → HCID 75967836, compound

HRID 2410202Notes

Reaction equation

HRID 2410202 reaction equation
[CH:1]([C:5]1[C:6]([OH:24])=[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].[CH:25](C1C(O)=C(C=C(/C=C/C(=O)C2C=CC(C)=CC=2)C=1)C=O)(CC)C.[C:49]([O:57][CH2:58]C)(=[O:56])[CH2:50][C:51]([O:53]CC)=O.N1C=CC=CC=1>O1CCCC1>[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:6]=1[O:24][C:51](=[O:53])[C:50]([C:49]([O:57][CH3:58])=[O:56])=[CH:25]2)([CH2:3][CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 1049PyridineHCID 7761Diethyl MalonateHCID 56653338HCID 56653338, compoundHCID 86692171HCID 86692171, compound

Product 1

HCID 75967836HCID 75967836, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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), diethyl malonate (0.23 g, 1.46 mmol) in tetrahydrofuran (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 dilute HCl (2 N). To this residue water (30 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, which upon concentration provides ethyl 8-sec-butyl-6-(3-(4-chlorophenyl)-3-oxoprop-1-enyl)-2-oxo-2H-chromene-carboxylate (General Formula IV). (0.51 g, 81% yield). White solid, m. p. 119-120° C.; 1H NMR (CDCl3, 300 MHz): δ 8.55 (s, 1H), 7.99 (d, 2H, J=8.6 Hz), 7.84-7.73 (m, 3H), 7.54-7.47 (m, 3H), 4.43 (q, 2H, J=7.1 Hz), 3.45-3.35 (m, 1H), 1.78-1.69 (m, 2H), 1.41 (t, 3H, J=7.1 Hz), 1.32 (d, 3H, J=7.0 Hz), 0.89 (t, 3H, J=7.3 Hz)); 13C NMR (CDCl3, 75 MHz): δ 188.6, 163.9, 156.2, 154.0, 148.5, 143.2, 139.5, 136.8, 136.3, 131.5, 131.4, 130.0, 129.1, 127.3, 122.3, 118.8, 118.2, 62.1, 33.5, 29.7, 20.4, 14.3, 12.0; ESI-MS (m/z): 439 (M+H)+.

Workup

  1. temperaturerefluxed
  2. customMost of the excess solvent was evaporated under reduced pressure
  3. additionTo this residue water (30 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, which upon concentration

Sources & evidence

ORD record
ord-376c59dd0a334d97b844ad168e053804
Source dataset
uspto-grants-2014_08
Patent number
US08815940B2

Reaction notes

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