反应详情

4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid (14.7 kg) obtained in Example 3, tetrahydrofuran (147 L), dimethylformamide (118 L) and 1-hydroxybenzotriazole (7.9 kg) were added at 20–25° C. to a 1500-L glass-lined vessel. And then, 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (13.6 kg) was added and stirred for 3 hours at this temperature. The reaction mixture was cooled to below 10° C., and then ethyl acetate (480 L) and water (120 L) were added dropwise at below 25° C. After cooling to 2–7° C., the slurry was stirred for 1 hour at this temperature. The product was collected on a stainless centrifuge and washed with acetonitrile (74 L). The damp solid was dried in a stainless vacuum dryer under vacuum to give 1-[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyloxy]-1H-1,2,3-benzotriazole (18.6 kg).

1. temperatureThe reaction mixture was cooled to below 10° C.
2. temperatureAfter cooling to 2–7° C.
3. stirringthe slurry was stirred for 1 hour at this temperature
4. customThe product was collected on a stainless centrifuge
5. washwashed with acetonitrile (74 L)
6. customThe damp solid was dried in a stainless vacuum dryer under vacuum