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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence