反应详情

N-methylazepan-4-one.HCl (50 mg, 0.30 mmol) and 4-nitrobenzaldehyde were dissolved in acetic acid (5 mL) and stirred for 10 min, then conc. H2SO4 (50 μL) was added slowly and the mixture was stirred at rt overnight. More concentrated H2SO4 (100 μL) was added and stirring was continued at rt for 6 h. Additional 500 μL of concentrated H2SO4 was added and the reaction stirred overnight. A further 350 μL of conc. H2SO4 was added and stirring continued for additional 5 h, during which period further H2SO4 was added in two portions (500 μL and 250 μL). Then water (3× reaction volume) was added and the mixture was stirred until rt was reached. The reaction mixture was extracted with ethyl acetate (3× reaction volume). The phases were separated and the organic phase concentrated to yield a dark yellow viscous oil. The crude product was purified by preparative HPLC, (XBridge column; eluents 50 mM ammonium carbonate buffer at pH 10 and methanol) giving the title product as a yellow solid (26.3 mg). LCMS System A: Rt 1.87 m/z [M+H]+ 394.1, System B: Rt 2.57.

1. stirringthe mixture was stirred at rt overnight
2. stirringstirring
3. waitwas continued at rt for 6 h
4. stirringthe reaction stirred overnight
5. stirringstirring
6. additionwas added in two portions (500 μL and 250 μL)
7. stirringthe mixture was stirred until rt
8. extractionThe reaction mixture was extracted with ethyl acetate (3× reaction volume)
9. customThe phases were separated
10. concentrationthe organic phase concentrated
11. customto yield a dark yellow viscous oil
12. customThe crude product was purified by preparative HPLC, (XBridge column; eluents 50 mM ammonium carbonate buffer at pH 10 and methanol)