反应详情

To a solution of 2-bromopyridine (0.89 g, 5.62 mmol) in THF (10 mL) at −78° C. was added n-BuLi (2.81 mL, 1.6 M in THF, 5.62 mmol). The reaction was stirred for 30 minutes prior to the addition of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (0.77 g, 2.81 mmol) as a solution in 5 mL of THF. The reaction was then stirred at room temperature for 30 minutes and then 1 hour at 60° C. The reaction was then quenched by adding a saturated solution of sodium bicarbonate and then extracted with 2×50 mL ethyl acetate. The combined organic layers was dried on magnesium sulfate and concentrated under vacuum to afford an orange oily solid which was purified via silica gel chromatography (gradient: ethyl acetate/hexane; 0:1 to 3:5) to afford the title compound as a white solid (290 mg). 1H NMR (400 MHz, CDC3) δ 8.70 (d, J=6.6 Hz, 1H), 8.05 (d, J=8.6 Hz, 1H), 7.86 (t, J=7.6 Hz, 1H), 7.46 (t, J=6.2 Hz, 1H), 4.25-4.13 (m, 2H), 4.09-4.00 (m, 1H), 2.94 (t, J=12.6 Hz, 2H), 1.91 (d, J=11.6 Hz, 2H), 1.69-1.65 (m, 2H), 1.50 (s, 9H). LRMS m/z ES+=290.8 (M+H), retention time 1.78.

1. stirringThe reaction was then stirred at room temperature for 30 minutes
2. custom1 hour
3. customat 60° C
4. customThe reaction was then quenched
5. additionby adding a saturated solution of sodium bicarbonate
6. extractionextracted with 2×50 mL ethyl acetate
7. customThe combined organic layers was dried on magnesium sulfate
8. concentrationconcentrated under vacuum
9. customto afford an orange oily solid which
10. customwas purified via silica gel chromatography (gradient: ethyl acetate/hexane; 0:1 to 3:5)