Potassium Phosphate, Tribasic → Ethyl 3-(2-aminopyridin-4-yloxy)-4-chlorobenzoate

Participants

Reaction Conditions

Reaction Steps

A flask was charged with ethyl 4-chloro-3-(2-chloropyridin-4-yloxy)benzoate (16.347 g, 52.369 mmol), tert-butyl carbamate (18.405 g, 157.11 mmol), potassium phosphate (12.228 g, 57.606 mmol), and toluene (150 mL). The flask was degassed with nitrogen, and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (3.0302 g, 5.2369 mmol) and tris(dibenzylideneacetone)dipalladium (0) (2.3978 g, 2.6185 mmol) were added. The flask was degassed again, and degassed water (40 mL) was added. The reaction was heated at 90° C. overnight. Water was added and the reaction mixture was extracted with ethyl acetate and concentrated. TFA (100 mL) was added and the mixture was stirred overnight, then concentrated, treated with sodium bicarbonate, and extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was purified by silica gel column chromatography eluting with 20-25% ethyl acetate in hexanes and then ethyl acetate to provide the desired product (5.75 g, 37.510% yield) as yellow oily semi solid.

Provenance & Evidence