Sodium hydride → tert-Butyl 4-cyano-4-(pyridin-3-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A flask was charged with sodium hydride (5.08 g, 127 mmol) and dimethylformamide (100 ml) at 0° C. under nitrogen. 2-(Pyridin-3-yl)acetonitrile (5 g, 42.3 mmol) was added in 25 mL of dimethylformamide via addition funnel over 20 min. After 20 min, tert-butyl bis(2-chloroethyl)carbamate (12.81 g, 52.9 mmol) was added in 20 mL of dimethylformamide via addition funnel over 20 min. The reaction was allowed to stir at 0° C. for 2 h and then at 60° C. for 12 h. The reaction was quenched with 10% sodium bicarbonate (100 mL) and extracted with ethyl acetate (5×100 mL). The organics were collected, washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified via column chromatography (10% 2M ammonia in methanol, 90% dichloromethane) to yield 7.5 g (49%) of desired product. Mass Spec.: 288.20 (MH)+. LC tr=1.380 min (Phenomenex-Luna 4.6×50 mm S10, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA Gradient Time=2 min, Flow rate=4 mL/min)

Provenance & Evidence