反应详情

温度

110 °C

A solution of 1.4 g (4.3 mMol) 6-(2-chloro-pyrimidin-4-yloxy)-benzo[d]isoxazole-3-carboxylic acid ethyl ester (Step 4.1) in 32 ml dioxane is degassed repeatedly by evaporation and flushing with N2. Then 2.1 g (6.44 mMol) Cs2CO3, 77 mg (0.13 mMol) 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 39.3 mg (0.0429 mMol) tris(dibenzylidenaceton)dipalladium(0) and 603 mg (5.15 mMol) carbamic acid tert-butyl ester are added successively. After 4.5 h stirring at 110° C., the mixture is cooled to rt and another 77 mg 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 39.7 mg tris(dibenzylidenaceton)dipalladium(0), 603 mg carbamic acid tert-butyl ester and 2.1 g Cs2CO3 are added and stirring is continued for 5 h. Then the cooled mixture is poured into EtOAc and water, the aq. layer separated off and extracted with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated together with 8 g SiO2. The resulting powder is put on top of a chromatography column (SiO2; CH2Cl2) and the title compound eluted with CH2Cl2→CH2Cl2/EtOAc 4:1: MS: [M+1]+=401; HPLC: tRet=15.4.

1. customflushing with N2
2. temperaturethe mixture is cooled to rt
3. stirringstirring
4. waitis continued for 5 h
5. customthe aq. layer separated off
6. extractionextracted with EtOAc
7. washThe organic layers are washed with water and brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated together with 8 g SiO2
10. washthe title compound eluted with CH2Cl2→CH2Cl2/EtOAc 4:1