N,N,N',N'-Tetramethylethylenediamine → HCID 19926679, compound

HRID 1647259Notes

Reaction equation

HRID 1647259 reaction equation
C(N(CC)[C:4](=[O:14])[C:5]1C=CC(C)=[CH:7][C:6]=1[O:12][CH3:13])C.CN(C)CCN(C)C.[C:25]([Li])([CH3:28])([CH3:27])[CH3:26].[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][C:33]=1[CH:34]=[O:35]>O1CCCC1.O>[CH3:26][C:25]1[CH:28]=[CH:7][C:6]([O:12][CH3:13])=[C:5]2[C:27]=1[CH:34]([C:33]1[CH:36]=[C:37]([O:40][CH3:41])[CH:38]=[CH:39][C:32]=1[O:31][CH3:30])[O:35][C:4]2=[O:14]

Participants

7

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 667262,5-DimethoxybenzaldehydeHCID 10987825HCID 10987825, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 19926679HCID 19926679, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

2-Methoxy-4-methylbenzoic acid diethyl amide (27 g) was dissolved in dry tetrahydrofuran (250 ml) with tetramethylethylenediamine (15 g). The solution was stirred under nitrogen and cooled to -70° C. Tert-Butyl lithium (1.7N in pentane, 100 ml) was added over 15 minutes and the solution was stirred for 45 minutes. 2,5-Dimethoxybenzaldehyde (20 g) in dry tetrahydrofuran (80 ml) was added over 10 minutes. The reaction mixture was stirred for one hour at -70° C. and then allowed to warm to room temperature. After 30 minutes water (10 ml) was added and the reaction mixture was concentrated down under reduced pressure. The resulting slurry was taken up in ethyl acetate (300 ml) and washed with 0.5N HCl (aq) (300 ml) and brine. The organic phase was dried (MgSO4), filtered and concentrated to dry under reduced pressure. The resulting oil was dissolved in toluene, para-toluenesulfonic acid (1 g) was added and the solution was heated under reflux for 3 hours. The solution was allowed to cool, washed with 1N NaHCO3 (aq), dried (MgSO4) and filtered. The solution was evaporated to dryness under reduced pressure. The resulting solid was dissolved in ethyl acetate (250 ml) and hexane was added (150 ml). The solution was allowed to stand over night at -20° C. The resulting precipitate was collected by filtration and dried to give 4-methyl-7-methoxy-3-(2',5'-dimethoxyphenyl)-1-(3H)-isobenzofuranone, m.p. 121°-123° C.

Workup

  1. stirringthe solution was stirred for 45 minutes
  2. stirringThe reaction mixture was stirred for one hour at -70° C.
  3. temperatureto warm to room temperature
  4. concentrationthe reaction mixture was concentrated down under reduced pressure
  5. washwashed with 0.5N HCl (aq) (300 ml) and brine
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto dry under reduced pressure
  10. dissolutionThe resulting oil was dissolved in toluene
  11. additionpara-toluenesulfonic acid (1 g) was added
  12. temperaturethe solution was heated
  13. temperatureunder reflux for 3 hours
  14. temperatureto cool
  15. washwashed with 1N NaHCO3 (aq)
  16. dry with materialdried (MgSO4)
  17. filtrationfiltered
  18. customThe solution was evaporated to dryness under reduced pressure
  19. dissolutionThe resulting solid was dissolved in ethyl acetate (250 ml)
  20. additionhexane was added (150 ml)
  21. waitto stand over night at -20° C
  22. filtrationThe resulting precipitate was collected by filtration
  23. customdried

Sources & evidence

ORD record
ord-665989f4099146249a086b64cb5090f9
Source dataset
uspto-grants-1995_07
Patent number
US05430067

Reaction notes

Loading…