反应详情

4-Methoxybenzaldehyde (5.63 mL, 46.4 mmol) and cyclobutanamine (3.3 g, 46.4 mmol) in dichloromethane (40 mL) were stirred at room temperature. After 45 min., magnesium perchlorate (0.231 g, 2.320 mmol) was added, and the reaction mixture was stirred at room temperature. After 16 hours, the reaction mixture was treated with Na2SO4 (2 g) and stirred at room temperature for 2 hours, filtered and concentrated to dryness. The reaction mixture was dissolved in methanol (40 mL), cooled to 0° C., and NaBH4 (1.6 g, 69.6 mmol) was added. After 15 min., the reaction mixture was warmed to room temperature. After 2 hours, the reaction mixture was diluted with 1N NaOH (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to isolate 4A (8.5 g, 82% yield) as a clear oil. HPLC: Rt=0.82 min (PHENOMENEX® Luna 5 micron C18 4.6×30 mm, 10-90% aqueous methanol containing 0.1% TFA, 2 min gradient, flow rate=5 mL/min, detection at 254 nm). MS (ES): m/z=192.6 [M+H]+.

1. waitAfter 16 hours
2. stirringstirred at room temperature for 2 hours
3. filtrationfiltered
4. concentrationconcentrated to dryness
5. dissolutionThe reaction mixture was dissolved in methanol (40 mL)
6. temperaturecooled to 0° C.
7. waitAfter 15 min.
8. temperaturethe reaction mixture was warmed to room temperature
9. waitAfter 2 hours
10. extractionextracted with ethyl acetate (3×100 mL)
11. dry with materialThe combined organic layers were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated