反应详情

To a solution of 3-(4-(1-benzhydryl-3-fluoroazetidin-3-yl)-3-bromophenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 29, 515 mg, 0.76 mmol) in MeCN/DCM (5:1, 60 mL) at 0° C. was added 1-chloroethyl chloroformate (275 uL, 2.5 mmol). The reaction was heated to reflux for 3 hours then allowed to cool to room temperature while stirring for 18 hours. Next, the reaction mixture was concentrated under vacuum, re-dissolved in anhydrous MeOH (50 mL), and refluxed for 1 hour. The reaction was cooled, concentrated under reduced pressure, and diethyl ether was added to residue. The resulting precipitate was filtered, rinsed with diethyl ether, and air dried to afford the intermediate (365 mg, 87%) as a solid. M/z (Cl) 713 ([M+H]+.

1. temperatureThe reaction was heated
2. temperatureto reflux for 3 hours
3. concentrationNext, the reaction mixture was concentrated under vacuum
4. dissolutionre-dissolved in anhydrous MeOH (50 mL)
5. temperaturerefluxed for 1 hour
6. temperatureThe reaction was cooled
7. concentrationconcentrated under reduced pressure, and diethyl ether
8. additionwas added to residue
9. filtrationThe resulting precipitate was filtered
10. washrinsed with diethyl ether, and air
11. customdried