Ammonium Chloride → HCID 71008574, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 5-(2-azetidin-1-yl-1,1-dimethyl-ethoxy)-2-chloro-pyridin (21.2 g, 88.1 mmol) in anhydrous tetrahydrofuran (314 ml) was added 2-(dicyclohexylphosphino)biphenyl (6.17 g, 17.6 mmol) and tris(dibenzylideneacetone)dipalladium(0) (8.06 g, 8.81 mmol). Then a solution of 1 M lithium bis(trimethylsilyl)amide in THF (264 ml, 264 mmol) was added via addition funnel over 5 minutes. The reaction mixture was stirred under argon atmosphere at 75° C. over-night. The reaction mixture was poured into a saturated solution of aqueous ammonium chloride (400 ml) and extracted with ethyl acetate (350 ml). The organic phase was collected and washed with 50% diluted brine (350 ml). The organic phase was collected and the aqueous phases were back extracted with ethyl acetate (2×200 ml). The combined organics were dried from magnesium sulfate, filtered and stripped. The remainder was purified by Analogix flash column chromatography (80 g column), eluting with 0% to 12% methanol in dichloromethane to provide the desired 5-(2-azetidin-1-yl-1,1-dimethyl-ethoxy)-pyridin-2-ylamine (10.59 g) as a dark brown semi-viscous oil (as well as a less-pure fraction which could be re-purified under similar conditions to provide another 4.01 g of product). LC/MS calc'd for C12H19N3O (m/e) 221.3, obs'd 222 (M+H, ES+).

Provenance & Evidence