Sodium hydride → Tert-butyl 4-cyano-4-(4-fluorophenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

2-(4-Fluorophenyl)acetonitrile (1.35 g, 10.0 mmol) and tert-butyl bis(2-chloroethyl)carbamate (2.42 g, 10.0 mmol) were combined in dimethylformamide (30 mL) and cooled to 0° C. The reaction was treated with sodium hydride (760 mg, 30.0 mmol) in several portions. The ice bath was removed and the reaction heated at 60° C. for 24 h. After cooling to room temperature, the mixture was poured into ice water and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (15% ethyl acetate/hexanes) gave 1.65 g (54%). 1H-NMR (CDCl3, 500 MHz) δ 7.39-7.44 (m, 2H), 7.04-7.10 (m, 2H), 4.23-4.27 (m, 2H), 3.12-3.21 (m, 2H), 2.03-2.07 (m, 2H), 1.82-1.92 (m, 2H), 1.45 (s, 9H). Mass spec.: 327.11 (MNa)+.

Provenance & Evidence