Isopropanol → 1-Benzyl-4-(ethylamino)piperidine-4-carbonitrile

Participants

Reaction Steps

To a solution of 4-N-benzylpiperidone (5.69 g, 29.5 mmol) in ethanol (4.2 ml) cooled in an ice bath was added ethylamine hydrochloride (2.69 g, 32.3 mmol) in water (3 ml), keeping the internal temperature of the reaction below 10° C. A solution of KCN (2.04 g, 31.3 mmol) in water (7 ml) was added to the reaction solution over 10 minutes while keeping the internal temperature below 10° C. The reaction was then warmed to room temperature and stirred 18 hours. Isopropanol (10 ml) was added to the reaction mixture to give two distinct layers: lower colorless aqueous layer and an orange organic upper layer. The organic layer was separated and stirred with water (30 ml) for 30 minutes. The organic layer was separated (orange organic layer now the bottom layer), the solvent was removed in vacuo, and the resultant oil diluted in methylene chloride (30 ml). The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated, in vacuo, to give I-1A-1e as an orange oil (6.05 g, 84%): +APcI MS (M+1) 244.2; 1H NMR (400 MHz, CD2Cl2) δ 7.32 (d, J=4.1 Hz, 4H), 7.29–7.23 (m, 1H), 3.54 (s, 2H), 2.81–2.76 (m, 2H), 2.75 (q, J=7.1 Hz, 2H), 2.35–2.29 (m, 2H), 2.01–1.98 (m, 2H), 1.74–1.68 (m, 2H), 1.14 (t, J=7.1 Hz, 3H).

Provenance & Evidence