反应详情

To a solution of 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol (Preparation 62B, 0.465 g, 1.740 mmol) in dichloromethane (9.0 mL) at 0° C. was added a 1.0 M solution of tribromophosphine in dichloromethane (2.09 mL, 2.09 mmol). After 5 min., the ice-bath was removed, and the reaction mixture was stirred at room temperature overnight. HPLC and LCMS analysis indicated that there was still significant starting material remaining. Additional tribromophosphine (1.0 M in dichloromethane) (2.09 mL, 2.09 mmol) was added, and the reaction mixture was stirred at room temperature for 4.5 h. Additional tribromophosphine (1.0 M in dichloromethane) (2.09 mL, 2.09 mmol) was added, and the reaction mixture was stirred at room temperature over the weekend. The reaction mixture was diluted with dichloromethane, washed with a saturated aqueous solution of sodium bicarbonate, and dried over anhydrous sodium sulfate. Concentration under reduced pressure provided the crude product, which was loaded with a minimum amount of dichloromethane on a fitted funnel containing a layer of Celite topped with a layer of silica gel. The plug column was eluted with a mixture of ethyl acetate and hexane (1%-3%) to give 3-(3-bromoprop-1-ynyl)-5-phenyl-4-(trifluoromethyl)isoxazole (0.219 g, 0.663 mmol, 38% yield) as a clear, colorless oil. The product had an HPLC ret. time=2.95 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=331.93.

1. customthe ice-bath was removed
2. stirringthe reaction mixture was stirred at room temperature for 4.5 h
3. stirringthe reaction mixture was stirred at room temperature over the weekend
4. washwashed with a saturated aqueous solution of sodium bicarbonate
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationConcentration under reduced pressure
7. customprovided the crude product, which
8. additioncontaining a layer of Celite
9. washThe plug column was eluted with a mixture of ethyl acetate and hexane (1%-3%)