反应详情

A mixture of 1-(4-bromophenyl)cyclobutanecarboxylic acid (200 mg, 0.78 mmol), diphenylphosphoryl azide (202 μL, 0.94 mmol), and triethylamine (131 μL, 0.94 mmol) in toluene (3 mL) was heated under reflux with stirring for 2 h. To the reaction mixture was added concentrated hydrochloric acid (1 mL). The resulting mixture was heated under reflux with stirring for 3 h. Then an ammonium hydroxide solution (5 mL) was added to the reaction mixture and the whole was extracted with ethyl acetate (15 mL×3). The combined organic phase was washed with brine (30 mL) and concentrated to give [1-(4-bromophenyl)cyclopropyl]amine as black oil. The crude amine was reacted with 5-chloro-2-(3-fluorophenoxy)nicotinic acid (step 1 of Example 128) according to the procedure described in step 3 of Example 1 to give the title compound: 1H-NMR (CDCl3) δ 8.47 (1H, d, J=2.4 Hz), 8.24 (1H, br.s), 8.14 (1H, d, J=2.4 Hz), 7.51–6.92 (8H, m), 2.74–1.43 (6H, m); MS (ESI) m/z 475 (M+H)+, 473 (M−H)−.

1. temperaturewas heated
2. temperatureunder reflux
3. temperatureThe resulting mixture was heated
4. temperatureunder reflux
5. stirringwith stirring for 3 h
6. extractionthe whole was extracted with ethyl acetate (15 mL×3)
7. washThe combined organic phase was washed with brine (30 mL)
8. concentrationconcentrated