3-Hydroxyazetidine hydrochloride → HCID 178480268, compound

Participants

Reaction Steps

To a mixture of Example 9H (100 mg, 0.245 mmol) and azetidin-3-ol hydrochloride (53.8 mg, 0.491 mmol) in pH 4 buffer solution (4 mL) (acetic acid and sodium acetate in MeOH) was added sodium cyanoborohydride (31 mg, 0.49 mmol) portion wise. The mixture was stirred at ambient temperature for 2 hours then concentrated under reduced pressure. The residue was dissolved in EtOAc and washed with saturated aqueous NaHCO3 and brine. The organic extract was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the residue by HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:10 mM ammonium acetate over 8 min (10 min run time) at a flow rate of 40 mL/min to afford 37.1 mg (32.5%) of the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 0.49-0.68 (m, 4H), 1.05-1.19 (m, 1H), 1.48 (s, 9H), 3.94 (s, 3H), 4.02-4.12 (m, 2H), 4.12-4.22 (m, 2H), 4.29 (d, J=7.12 Hz, 2H), 4.49-4.59 (m, 1H), 4.70 (s, 2H), 5.07 (s, 1H), 6.93 (s, 1H), 7.64-7.69 (m, 2H), 8.33 (s, 1H); MS (ESI) m/z 465 [M+H]+, 463[M−H]−.

Provenance & Evidence