反应详情

To a stirred suspension of ethyl 7-(4-(2-bromo-4-chlorophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (129 mg; 0.22 mmol) in 2 mL toluene was added successively water (0.1 mL), potassium phosphate (138 mg; 0.65 mmol), tricyclohexylphosphine (24 mg; 0.087 mmol), and cyclopropylboronic acid (0.435 mmol) at ambient temperature with stirring. A balloon of nitrogen with a three-way purge valve was attached, and the flask was evacuated and refilled five times with nitrogen. Palladium (II) acetate (10 mg; 0.043 mmol) was added, and again the flask was evacuated and refilled five times with nitrogen. The mixture was stirred in an oil bath set to 100° C. under the nitrogen balloon. After 4 hours the mixture was cooled to ambient temperature. The mixture was diluted with 10 mL EtOAc and 5 mL water. The mixture was transferred to a separatory funnel and after shaking, the organic layer was separated, dried over sodium sulfate and evaporated to give a brown oil. This material was purified by silica gel chromatography on a Biotage 25S column, eluting with 75/25 hexane/EtOAc to provide 83 mg of ethyl 6-chloro-7-(4-(4-chloro-2-cyclopropylphenethylcarbamoyl)phenoxy)chroman-4-carboxylate as a colorless oil. MS (apci, pos) m/z=554.

1. customA balloon of nitrogen with a three-way purge valve
2. customthe flask was evacuated
3. additionrefilled five times with nitrogen
4. customagain the flask was evacuated
5. additionrefilled five times with nitrogen
6. stirringThe mixture was stirred in an oil bath
7. customset to 100° C. under the nitrogen balloon
8. additionThe mixture was diluted with 10 mL EtOAc and 5 mL water
9. customThe mixture was transferred to a separatory funnel
10. stirringafter shaking
11. customthe organic layer was separated
12. dry with materialdried over sodium sulfate
13. customevaporated
14. customto give a brown oil
15. customThis material was purified by silica gel chromatography on a Biotage 25S column
16. washeluting with 75/25 hexane/EtOAc