5-(trifluoromethyl)benzo[d]isoxazol-3-amine synthesis

Yield:868271-14-1 76.7%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 80;

Steps:

5-Trifluoromethyl-benzo[d]isoxazol-3-ylamine

2-Fluoro-5-trifluoro-benzonitrile (Matrix, 5 g, 26.4 mmol), N-hydroxy-acetamide (Aldrich, 2.9 g, 39.7 mmol) and K₂CO₃ (5.48 g, 39.7 mmol) in DMF (20 mL) were heated at 80 °C overnight. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous Na₂SO₄, filtered and concentrated to give the crude material, which was purified by silica gel column (hexanes: ethyl acetate 2:1 ) to afford the title compound as white solid (4.1 g, 76.7%). MS: 203 (MH⁺).

References:

Zhang, Xuqing;Hufnagel, Heather;Hou, Cuifen;Opas, Evan;McKenney, Sandra;Crysler, Carl;O'Neill, John;Johnson, Dana;Sui, Zhihua [Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,# 20,p. 6042 - 6048] Location in patent:supporting information; experimental part