Acetic Acid → HCID 66996118, compound

Participants

Reaction Steps

A mixture of 4-formylbenzonitrile (510 mg, 3.89 mmol), methyl azetidine-3-carboxylate (590 mg, 3.89 mmol), acetic acid (0.245 mL, 4.28 mmol) and ˜1 gm of powdered 4 Angstrom molecular sieves in DCE (15 mL) was stirred briskly at RT for 1 hr. At this time, sodium triacetoxyborohydride (907 mg, 4.28 mmol) was added and the reaction mixture was stirred at RT for 2 hr. After filtering through a sintered glass funnel, the filtrate was concentrated to a residue that was partitioned between EtOAc (50 mL) and saturated sodium bicarbonate solution (50 mL). The organic layer was washed with brine (50 mL), dried (MgSO4) and concentrated to afford a colorless oil that was chromatographed on a 12 gm Isco silica gel cartridge, eluting with a 0-100% EtOAc/Hex gradient. The essentially pure fractions were concentrated to afford methyl 1-(4-cyanobenzyl)azetidine-3-carboxylate (765 mg, 3.32 mmol). HPLC retention time=0.49 minutes [broad peak] (PHENOMENEX® Luna 4.6×30 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.1% TFA over a 2 minute gradient. MS:(M+H)=231.23. 1H NMR (400 MHz, CDCl3) δ ppm 3.32-3.36 (m, 3H) 3.49-3.58 (m, 2H) 3.67 (s, 2H) 3.72 (s, 3H), 7.39 (d, J=8.6 Hz, 2H) 7.60 (d, J=8.3 Hz, 2H).

Provenance & Evidence