反应详情

温度

-20 °C

To a solution of methyl 4-oxo-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (8.75 g, 27.75 mmol) (Syngene) in DME (100 mL) under nitrogen was added simultaneously 1-(isocyanomethylsulfonyl)-4-methylbenzene (8.13 g, 41.63 mmol) in 100 mL DME and potassium tert-butoxide (83 mL, 83.26 mmol) (1 M) over 30 min at −20 to −10° C. The solution was stirred at −20° C. for 2 h and then allowed to warm to room temperature overnight. To the orange reaction mixture was added water (200 mL), the solution was stirred for 20 min and then extracted with diethyl ether (3×) and EtOAc (3×). The combined organic phases were washed once with brine and then dried over Na2SO4 and evaporated to yield a brown oil. The oil was purified by flash chromatography on silica gel using a gradient of 20-60% EtOAc in heptane as eluent. Methyl 4-cyano-2-(4-(trifluoromethyl)benzyl)piperidine-1-carboxylate (7.96 g, 87.9%) was isolated as a yellow oil.

1. temperatureto warm to room temperature overnight
2. stirringthe solution was stirred for 20 min
3. extractionextracted with diethyl ether (3×) and EtOAc (3×)
4. washThe combined organic phases were washed once with brine
5. dry with materialdried over Na2SO4
6. customevaporated
7. customto yield a brown oil
8. customThe oil was purified by flash chromatography on silica gel using a gradient of 20-60% EtOAc in heptane as eluent