Hydrochloric Acid → 3-Hydroxy-4-isobutyryl-2-oxo-1-phenyl-2,5-dihydropyrrole

HRID 234723Notes

Reaction equation

HRID 234723 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:9][CH:10]([CH3:21])[C:11](=[O:20])[CH2:12][C:13](=[O:19])[C:14]([O:16]CC)=O.[CH2:22]=O>C(O)C.CC(C)=O>[OH:19][C:13]1[C:14](=[O:16])[N:1]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:22][C:12]=1[C:11](=[O:20])[CH:10]([CH3:9])[CH3:21]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 6115AnilineHCID 3017501Ethyl 5-methyl-2,4-dioxohexanoate

Product 1

HCID 153380843-Hydroxy-4-isobutyryl-2-oxo-1-phenyl-2,5-dihydropyrroleYield 31.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 702EthanolSolvent

Procedure

To a stirred mixture of aniline (0.50 g, 5.4 mmole) and concentrated HCl (0.46 ml) in ethanol (2.5 ml) was added ethyl 5-methyl-2,4-dioxohexanoate (1.0 g, 5.4 mmole) and paraformaldehyde (0.25 g). After heating at reflux over 3 hours hot acetone (13 ml) was added and the resulting solution was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in 1N NaOH and extracted with methylene chloride. The aqueous layer was acidified to pH 1 with 3N HCl, extracted with methylene chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. Recrystallization from 10% ether in pet. ether gives 0.42 g of the title compound as a pale yellow solid. M.P. 162°-170° C.; 1H NMR (250 MHz, CDCl3) δ1.21 (d, J=6.8 Hz, 6H), 3.24 (heptet, J=6.8 Hz, 1H), 4.52 (s, 2H), 7.23 (m, 1H), 7.43 (t, J=8.0 Hz, 2H), 7.77 (d, J=7.8 Hz); MS m/z 246.

Workup

  1. temperatureAfter heating
  2. additionwas added
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in 1N NaOH
  5. extractionextracted with methylene chloride
  6. extractionextracted with methylene chloride
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customRecrystallization from 10% ether in pet. ether

Sources & evidence

ORD record
ord-4091769180174d55bc0cda058c2f258b
Source dataset
uspto-grants-1997_01
Patent number
US05596013

Reaction notes

Loading…