反应详情

温度

110 °C

To a mixture of azetidin-3-ol (CAN 45347-82-8, 200 mg, 3 mmol), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (CAS 98327-87-8, 114 mg, 0.185 mmol), tris(dibenzylideneacetone)dipalladium (CAS 51364-51-3, 85 mg, 0.1 mmol) and cesium carbonate (CAS 534-17-8, 1.8 mg, 5.55 mmol) in toluene (8 mL) under nitrogen atmosphere, was added a solution of 5-bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 9 d, 500 mg, 1.85 mmol). The reaction mixture was stirred overnight at 110° C. The reaction mixture was concentrated in vacuo and the residue dissolved in water and extracted with ethyl acetate (1×30 mL). The aqueous layer was adjusted to pH=2 by addition of 1 N hydrochloric acid, the resulting precipitate was collected by filtration, the solid was lyophilized. The crude product was purified by flash chromatography (silica gel, 50 g, 0% to 100% ethyl acetate in petroleum ether) to give the desired product (180 mg) as a yellow solid; MS (EI): m/e=265.2 [M+H]+.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionthe residue dissolved in water
3. extractionextracted with ethyl acetate (1×30 mL)
4. additionThe aqueous layer was adjusted to pH=2 by addition of 1 N hydrochloric acid
5. filtrationthe resulting precipitate was collected by filtration
6. customThe crude product was purified by flash chromatography (silica gel, 50 g, 0% to 100% ethyl acetate in petroleum ether)