4-(2-hydroxyethoxy)-3,5-dimethylbenzaldehyde

2233-18-3

107-07-3

1039948-89-4

General procedure for the synthesis of 3,5-dimethyl-4-hydroxybenzaldehyde from 3,5-dimethyl-4-hydroxybenzaldehyde and 2-chloroethanol: 1. In a 2L dry round bottom flask, add a solution of 3,5-dimethyl-4-hydroxybenzaldehyde (26.9 g, 0.179 mol) in ethanol (350 mL). 2. 2-Chloroethanol (87.6 g, 1.074 mol) and K2CO3 (99 g, 0.716 mol) were added and the reaction mixture was heated to reflux for 24 hours. 3. The reaction mixture was cooled to room temperature and filtered. The solvent was removed under reduced pressure. 4. The crude product was diluted with ethyl acetate and the organic layer was washed with water and brine and dried with Na2SO4. 5. After removing the solvent, 45g of crude product was obtained. 6. The crude product was purified by column chromatography (silica gel 230-400 mesh; 50% hexane solution of ethyl acetate as eluent) to give 33.3 g (95%) of product. Steps for the synthesis of 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one: 1. dissolve 2-amino-4,6-dimethoxybenzamide (33.45 g, 0.170 mol) and 4-(2-hydroxyethoxy)-3,5-dimethylbenzaldehyde (33.3 g, 0.170 mol) in N,N-dimethylacetamide (300 mL). 2. NaHSO3 (33.3 g, 0.187 mol) and p-TSA (3.2 g, 17.1 mmol) were added and the reaction mixture was heated at 150 °C for 14 hours. 3. The reaction was cooled to room temperature. The solvent was removed under reduced pressure. 4. The residue was diluted with water and stirred at room temperature for 30 min. 5. The separated solid was filtered and dried to give the crude product. 6. The crude product was purified by column chromatography (silica gel 230-400 mesh; CH2Cl2 solution in 5% methanol as eluent) to afford 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxyquinazolin-4(3H)-one (33 g, 52%).