反应详情

A 100-mL 3-necked round-bottom flask was charged with a solution of 3-(1H-pyrazol-5-yl)piperidine (1.8 g, 11.31 mmol, 1.00 equiv, 95%) in tetrahydrofuran (THF) (100 mL). To this was added 9-ethyl-9H-carbazole-2-carbaldehyde (2.66 g, 11.32 mmol, 1.02 equiv, 95%) and Ti(OiPr)4 (4.24 g, 14.76 mmol, 1.25 equiv, 99%). The resulting solution was allowed to stir at room temperature overnight. To the mixture was then added NaBH3CN (3 g, 47.26 mmol, 4.00 equiv, 99%). The resulting mixture was allowed to stir at room temperature overnight. The progress was monitored by TLC (DCM; MeOH=10:1). Upon completion, the reaction was quenched by the addition of saturated aqueous Na2CO3 (150 mL). The resulting mixture was extracted with ethyl acetate (5×200 mL). Combined organic layers were dried over MgSO4, filtered off and concentrated on a rotary evaporator to give a residue that was purified by silica gel column chromatography eluted with DCM/MeOH (50:1) affording 3-((3-(1H-pyrazol-5-yl)piperidin-1-yl)methyl)-9-ethyl-9H-carbazole as a white solid (0.211 g, 5%). LCMS: [M+H]+: 359.2. 1H NMR (CDCl3,300 MHz) δ 8.11 (m, 1H), 8.00 (s, 1H), 7.48-7.36 (m, 5H), 7.24 (m, 1H), 6.03 (s, 1H), 4.37 (m, 2H), 3.93 (br, 2H), 3.76 (s, 2H), 3.15-2.60 (m, 5H), 1.67-1.56 (m, 4H), 1.43 (t, 3H).

1. stirringto stir at room temperature overnight
2. customUpon completion, the reaction was quenched by the addition of saturated aqueous Na2CO3 (150 mL)
3. extractionThe resulting mixture was extracted with ethyl acetate (5×200 mL)
4. dry with materialCombined organic layers were dried over MgSO4
5. filtrationfiltered off
6. concentrationconcentrated on a rotary evaporator
7. customto give a residue that
8. customwas purified by silica gel column chromatography
9. washeluted with DCM/MeOH (50:1)