反应详情

A solution of tert-butyl 1-(4-cyano-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate (0.268 g, 0.787 mmol), hydroxylamine hydrochloride (0.109 g, 1.57 mmol), and sodium bicarbonate (0.265 g, 3.15 mmol) in isopropanol (2.2 mL) was stirred at 90° C. for 6.0 hrs. HPLC and LCMS indicated that the reaction was 69% complete. Additional hydroxylamine hydrochloride (0.109 g), sodium bicarbonate (0.265 g), and isopropanol (2.2 mL) were added, and heating was continued for 16 hrs. The isopropanol was removed under reduced pressure, and the reaction mixture was diluted with ethyl acetate and washed with water (2×), washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)-3-(trifluoromethyl)benzyl)azetidine-3-carboxylate (0.258 g, 0.690 mmol, 88% yield) of a colorless, viscous oil. The compound had an HPLC ret. time=0.880 min.−Column: PHENOMENEX® S5 4.6×30 mm (2 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=374.10.

1. temperatureheating
2. customThe isopropanol was removed under reduced pressure
3. additionthe reaction mixture was diluted with ethyl acetate
4. washwashed with water (2×)
5. washwashed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationConcentration under reduced pressure