反应详情

温度

80 °C

Under argon, trimethylsilyl polyphosphate (10.6 g) is dissolved in 75.7 ml absolute dioxane. To this solution are added 4-cyanobenzaldehyde (5.95 g, 45.4 mmol), 3-trifluoromethylphenyl thiourea (5 g, 22.7 mmol) and 2-cyanoethyl acetoacetate (6.4 g, 45.4 mmol). The reaction mixture is stirred at 80° C. for 3 hours. After evaporation of the dioxane solvent, the residue is dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution, 38% sodium bisulfite solution and saturated sodium chloride solution. After drying with magnesium sulfate and evaporating off the solvent, the residue is dissolved in 15 ml methanol and purified by preparative HPLC (column: Kromasil 100 C 185 μm, 30 mm×150 mm; precolumn: Gromsil ODS 4 HE 15 μm, 10 mm×20 mm; flow rate: 66 ml/min; solvent A: acetonitrile, solvent B: water; gradient: 0 min 10% A, 3 min 10% A, 11 min 90% A, 13 min 90% A, 13.2 min 10% A, 15 min 10% A; wavelength: 220 nm; injection volume: approx. 2000 μl; number of injections: 12). The product containing fractions are combined and concentrated in vacuo.

1. customAfter evaporation of the dioxane solvent
2. dissolutionthe residue is dissolved in ethyl acetate
3. washwashed with saturated aqueous sodium bicarbonate solution, 38% sodium bisulfite solution and saturated sodium chloride solution
4. dry with materialAfter drying with magnesium sulfate
5. customevaporating off the solvent
6. dissolutionthe residue is dissolved in 15 ml methanol
7. custompurified by preparative HPLC (column: Kromasil 100 C 185 μm, 30 mm×150 mm; precolumn: Gromsil ODS 4 HE 15 μm, 10 mm×20 mm; flow rate: 66 ml/min; solvent A: acetonitrile, solvent B: water; gradient: 0 min 10% A, 3 min 10% A, 11 min 90% A, 13 min 90% A, 13.2 min 10% A, 15 min 10% A; wavelength: 220 nm; injection volume: approx. 2000 μl; number of injections: 12)
8. additionThe product containing fractions
9. concentrationconcentrated in vacuo