HRID1961540

反应详情

EQUATION

反应方程式

HRID 1961540 的结构方程式

AUXILIARIES

试剂、催化剂与溶剂

1

CONDITIONS

反应条件

温度
-40 °C

PROCEDURE

实验过程

In an oven-dried flask containing 3-(3-bromo-4-iodophenyl)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazole (Preparation 27, 1000 mg, 1.67 mmol) in THF (25 mL) at −40° C. was slowly added isopropyl magnesium chloride (1.7 mL of 2.0M solution). The reaction was stirred at approx. −40° C. for 1.5 under nitrogen. 1-benzhydrylazetidin-3-one (520 mg in 4 mL THF) was slowly added. The reaction was stirred at −40° C. for an additional 30 minutes and allowed to warm to room temperature. Stirring was continued for 2 hours at room temperature. The reaction was quenched with saturated NH4Cl and extracted with EtOAc (2×75 mL). The combined organic phase was dried (Na2SO4) and concentrated under vacuum. The crude material was chromatographed (40 g Redi-Sep column) eluting from 100% heptane to 60:40 EtOAc:heptane, collecting the intermediate (615 mg, 52%) as a glass. 1HNMR (CDCl3): 7.87 (1H), 7.66-7.63 (3H), 7.45 (4H), 7.36-7.21 (7H), 4.39 (1H), 4.07 (1H), 3.73-3.58 (5H), 3.06 (1H); m/z (Cl) 711 ([M+H]+.

WORKUP

后处理

  1. stirringThe reaction was stirred at −40° C. for an additional 30 minutes
  2. temperatureto warm to room temperature
  3. stirringStirring
  4. customThe reaction was quenched with saturated NH4Cl
  5. extractionextracted with EtOAc (2×75 mL)
  6. dry with materialThe combined organic phase was dried (Na2SO4)
  7. concentrationconcentrated under vacuum
  8. customThe crude material was chromatographed (40 g Redi-Sep column)
  9. washeluting from 100% heptane to 60:40 EtOAc
  10. customheptane, collecting the intermediate (615 mg, 52%) as a glass