反应详情

1.0 g (3.7 mmol) of 4-methoxy-3-(4-methoxytetrahydrofuran-3-yloxy)benzoic acid (starting compound A1) is heated to reflux for 2 h in 4 ml of oxalyl chloride. Excess oxalyl chloride is removed in vacuo and coevaporated using 2×20 ml of toluene. A solution of 600 mg (3.7 mmol) of 4-amino-3,5-dichloropyridine in 10 ml of tetrahydrofuran is added dropwise to a suspension of 220 mg (7.4 mmol) of 80% strength sodium hydride in 10 ml of tetrahydrofuran. The mixture is stirred for 1 h at RT, the acid chloride is then added dropwise in a further 10 ml of tetrahydrofuran and the reaction mixture is stirred at RT overnight. It is concentrated, the residue is treated with 50 ml of water and the mixture is extracted with 3×50 ml of dichloromethane. The combined organic phases are dried over magnesium sulfate, concentrated and the residue is crystallized from 50 ml of isopropanol. 1.2 g of the title compound of m.p. 175-177° C. are obtained.

1. customExcess oxalyl chloride is removed in vacuo
2. stirringthe reaction mixture is stirred at RT overnight
3. concentrationIt is concentrated
4. additionthe residue is treated with 50 ml of water
5. extractionthe mixture is extracted with 3×50 ml of dichloromethane
6. dry with materialThe combined organic phases are dried over magnesium sulfate
7. concentrationconcentrated
8. customthe residue is crystallized from 50 ml of isopropanol