反应详情

温度

35 °C

A stirred solution of alcohol-amine title product of Example 3 (179.4 g, 1.05 mol), 3-chloro-1,2-benzo[d]-isoxazole (194.2 g, 1.26 mol), and 1,8-diazabicyclo-[5.4.0]undec-7ene (DBU, 197.9 g, 1.30 mol) in pyridine (400 ml) was heated at 100° C. for 18 hours. After cooling to 35° C., water (3 liters), methylene chloride (2.5 liters) and, finally, saturated aqueous sodium carbonate (2 liters) were added, and the resulting biphasic mixture was vigorously stirred for 3 hours. The tan solid precipitate which formed during the stirring period was filtered, and the filter cake was washed first with water and then with hexane (1 liter of each) prior to being dried in vacuo. Trituration of the entire sample (216 g) with isopropyl alcohol (630 ml) followed by filtration and in vacuo drying afforded present title compound (154.5 g, 51% yield) as a light tan powder, sufficiently pure for use in the next step without further purification. TLC Rf (methylene chloride/methanol=9:1 in volume; iodoplatinate spray): 0.50. 13CNMR (CDCl3) delta 164.0, 161.1, 129.5, 122.3, 122.1, 116.2, 110.5, 66.3, 60.3, 58.7, 54.3, 53.7, 48.3, 39.1, 29.0, 26.7.

1. customThe tan solid precipitate which formed during the stirring period
2. filtrationwas filtered
3. washthe filter cake was washed first with water
4. dry with materialwith hexane (1 liter of each) prior to being dried in vacuo
5. filtrationTrituration of the entire sample (216 g) with isopropyl alcohol (630 ml) followed by filtration and in vacuo
6. customdrying