Ammonium Chloride → HCID 90202341, compound

Participants

Reaction Steps

3-[4-(3-Fluoro-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid (which may be prepared as described in Preparation of Intermediate 5; 313 mg, 1.0 mmol) and diisopropylethylamine (275 μL, 1.6 mmol) were dissolved in CH2Cl2 (6 mL). N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (160 mg, 3 mmol), 1-hydroxybenzotriazole (180 mg, 1.16 mmol), and NH4Cl (53.5 mg, 3 mmol) were added. The reaction mixture was stirred at room temperature. DMF (6 mL) was added to the heterogeneous reaction mixture and the resulting solution was stirred at room temperature for 48 h. Additional equivalents of NH4Cl, 1-hydroxybenzotriazole, N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride, and diisopropylethylamine were added. The reaction mixture was stirred for an additional 48 h, and then purified by chromatography, eluting with 45% EtOAc/hexanes, to give 3-[4-(3-fluoro-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (65 mg, 21%), mp 221-222° C. LRMS (ESI+): m/z [M+H]+ 313.0. Impurity observed at m/z=423. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.34 (s, 1H), 7.98 (s, 1H), 7.84 (d, J=9.2 Hz, 2H), 7.52 (s, 1H), 7.42 (dd, J=8.1, 5.9 Hz, 1H), 7.29 (d, J=7.3 Hz, 2H), 7.15 (d, J=8.8 Hz, 3H), 5.20 (s, 2H).

Provenance & Evidence