Acetic Acid → HCID 71739075, compound

Participants

Reaction Steps

2-(6-Chloropyridin-3-yloxy)-2-methylpropanal [prepared according to US2012/40949 A1] (28 g, 140 mmol, Eq: 1.00) was taken up in dry dichloromethane (252 ml) and cooled to −10° C. (dry ice/acetonitrile cooling bath) under nitrogen atmosphere. Acetic acid (10.4 ml, 182 mmol) and sodium triacetoxyborohydride (41.6 g, 196 mmol) were added. Azetidine (17 ml, 252 mmol) was next added via drop-wise addition over 6 minutes, with efficient stirring. After complete addition the mixture was stirred for 5 minutes and then the cooling bath was removed and the material warmed to ambient. After 1 hour a saturated solution of aqueous sodium bicarbonate (200 ml) was added as well as dichloromethane (80 ml). The biphasic material was transferred to a separatory funnel, agitated and the organic phase was collected. This was shaken with a 5% solution of sodium bicarbonate (200 ml) and then a 50% diluted solution of brine (200 ml). The organic phase was collected and the aqueous phases were back extracted with methylene chloride (2 100 ml). The organic phase was combined, dried with magnesium sulfate, filtered and stripped. The crude remainder was purified via column chromatography (silica gel, 40 g) eluting with a 4% solution of methanol in dichloromethane to provide the desired 5-(2-azetidin-1-yl-1,1-dimethyl-ethoxy)-2-chloro-pyridin (29.66 g) as a golden brown mobile oil. LC/MS calc'd for C12H17ClN2O (m/e) 240.73, obs'd 241 (M+H, ES+).

Provenance & Evidence