1-Bromo-3-chloropropane → 1-(3-Chloropropyl)azetidine-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

In a 25 mL round-bottomed flask were mixed with stirring azetidine-3-carbonitrile hydrochloride (available from ASW MedChem. Inc., 250 mg, 2.11 mmol) and 1-bromo-3-chloropropane (664 mg, 415 μL, 4.22 mmol.0) in acetonitrile (5 mL) to the suspension was added Cs2CO3 (2.06 g, 6.33 mmol). The mixture was stirred at 25° C. for 18 h, then diluted with 15 mL of EtOAc and filtered to remove solids. Filtrate was evaporated and residue purified by chromatography (40 g column, 50 μm from Analogix, 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane (developing TLC in an iodine chamber) to give 1-(3-chloropropyl)azetidine-3-carbonitrile (230 mg, 1.45 mmol, 68.8%) as a clear dense liquid. 1H NMR (CDCl3) δ: 3.46-3.59 (m, 4H), 3.20-3.31 (m, 3H), 2.55 (t, J=6.8 Hz, 2H), 1.75 (quin, J=6.6 Hz, 2H).

Provenance & Evidence