A mixture of ethyl acetoacetate 52.0g (399 mmol), ethyl orthoformate 59.2g (399 mmol) and acetic anhydride 81.6g (800 mmol) in a 0.5L round flask was refluxed under nitrogen on a 150 C oil bath for 90 min. The reflux condenser was replaced with a shortpath distillation apparatus and the formed ethyl acetate was distilled out from the reaction mixture at atmospheric pressure under nitrogen from a 150C oil bath. (This took additional one hour). The cooled reaction mixture was then distilled at 6 Torr from an oil bath (30 C to 90 C) to remove the formed acetic acid. The distillation residue was then fractionally distilled on highvac. After a small fruity-smelling front fraction (few mL) the desired product distilled at 75-82 C/0.25 Torr.
The obtained main fraction of the product was re-distilled on highvac, b.p. 80 C/0.15 Torr. Y = 48.2g of a colorless slightly oily liquid. The pure product has only a faint (non-fruity) odor.
1H-NMR (CDCl3, 400MHz) shows two sets of closely-spaced signals of the E and Z isomers, approximately of equal height: 7.671(s, 0.5H), 7.639(s, 0.5H), 4.251(m, 4H), 2.407(s, 1.5H), 2.346(s, 1.5H), 1.402(m, 3H), 1.339(m, 6H)
Note: A condensation of this material (2.5 mmol) with the diaminotriazole (2.0 mmol) from the preceding experimental in AcOH 5 mL at RT (10 min) and then at 110 C (for one hour) followed by evaporation and precipitation of the residue with MeCN provided the following cyclization product in 76% Y.
1H(d6-DMSO, 400MHz): 10.353 (s, 1H), 9.010(s, 1H), 7.774(app d, 8.8Hz, 2H), 7.423(app d, 8.8 Hz, 2H), 4.370(q, 7.1Hz, 2H), 3.084(s, 3H), 2.976(s, 6H), 1.368(t, 7.1Hz, 3H)