Acetic Acid → HCID 45088250, compound

Participants

Reaction Steps

To a solution of 4-cyanopiperidine (2.5 g, 23 mmol, J. Org. Chem. 21, 984-986, 1957) in methanol (16 mL) and THF (65 mL) was added with stirring (1-ethoxycyclopropoxy)-trimethylsilane (7.0 g, 40 mmol), glacial acetic acid (2.3 mL) and sodium cyanoborohydride (3.3 g, 53 mmol). When addition was complete the mixture was stirred 1 h at ambient temperature and then heated overnight at 65° C. under an atmosphere of nitrogen. The solvent was evaporated and to the residue was added water (30 mL) and 1N HCl until pH 1. The mixture was washed with diethyl ether (50 mL) and the acidic aqueous phase was saturated with potassium carbonate. The alkaline mixture was extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried (MgSO4) and the solvent was evaporated. This afforded 3.2 g of 1-cyclopropyl-4-cyanopiperidine. 1H NMR (400 MHz, CDCl3) δ 0.37-0.50 (m, 4H), 1.59-1.66 (m, 1H), 1.77-1.94 (m, 4H), 2.4-2.9 (m, 5H).

Provenance & Evidence