反应详情

4-Iodobenzo trifluoride (2.97 g, 10.92 mmol) in THF (50 mL) was added dropwise over 0.5 h to a solution of n-BuLi (7.5 ml, 1.6 M, 12 mmol) in THF (50 mL) at −78° C. The reaction mixture was stirred an additional 0.5 h upon which N-benzyl-4-piperidone (2.13 g, 11.69 mmol) in THF (10 mL) was added over 10 minutes. Stirring was continued for 0.5 h at −78° C., followed by room temperature overnight. The reaction was quenched with saturated ammonium chloride and the organic layer was separated. The aqueous layer was extracted with THF and the combined organic layers were dried (MgSO4), filtered and concentrated to afford a brown oil. The crude product was then dissolved in conc. HCl (30 mL) and 1,4-dioxane (6 mL) and stirred at 100° C. overnight. The reaction was poured into saturated sodium bicarbonate and extracted with ethyl acetate (3×200 mL). The combined organic layers were dried (MgSO4), filtered and concentrated. The product was purified by silica gel flash column chromatography (20% ethyl acetate in hexanes) to afford 1-benzyl-4-(4-trifluoromethyl-phenyl)-1,2,3,6-tetrahydro-pyridine (981 mg, 28%). 1H NMR (400 MHz, CDCl3) δ 7.61 (d, 2H), 7.52 (d, 2H), 7.40 (m, 5H), 6.21 (m, 1H), 3.70 (s, 2H), 3.25 (q, 2H), 2.78 (t, 2H), 2.62 (m, 2H); LCMS: 318.4 (M+1)+.

1. additionwas added over 10 minutes
2. waitfollowed by room temperature overnight
3. customThe reaction was quenched with saturated ammonium chloride
4. customthe organic layer was separated
5. extractionThe aqueous layer was extracted with THF
6. dry with materialthe combined organic layers were dried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a brown oil
10. extractionextracted with ethyl acetate (3×200 mL)
11. dry with materialThe combined organic layers were dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customThe product was purified by silica gel flash column chromatography (20% ethyl acetate in hexanes)