Acetic Acid → HCID 66996118, compound

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).

1. stirringthe reaction mixture was stirred at RT for 2 hr
2. filtrationAfter filtering through a sintered glass funnel
3. concentrationthe filtrate was concentrated to a residue that
4. customwas partitioned between EtOAc (50 mL) and saturated sodium bicarbonate solution (50 mL)
5. washThe organic layer was washed with brine (50 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated
8. customto afford a colorless oil that
9. customwas chromatographed on a 12 gm Isco silica gel cartridge
10. washeluting with a 0-100% EtOAc/Hex gradient
11. concentrationThe essentially pure fractions were concentrated

ORD record

ord-e703f774863f40f19414cd0e2bf35fc4

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389509B2