反应详情

温度

52.5 °C

6-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinonitrile (58.8 g, 190 mmol) was suspended in water (440 mL) and ethanol (600 mL) and treated with 32% sodium hydroxide solution (178 mL 1.92 mol). The mixture was heated to 50-55° C. and subsequently stirred at this temperature for 15 hour. The slightly turbid mixture was polish filtered to remove the ether by-product 6-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxymethyl-3-(4-fluoro-phenyl)-5-methyl-isoxazole. The first vessel and the transfer lines were rinsed with a mixture of water (50 mL) and ethanol (50 mL). The filtrate was treated at 20-25° C. within one hour with 25% hydrochloric acid (approx. 280 mL) until the pH was <2.0. The resulting suspension was stirred for one hour at room temperature. The crystals were filtered off, washed with a mixture of ethanol (200 mL) and water (200 mL) and subsequently dried at 50° C./<25 mbar until constant weight to afford 52.0 g (83%) of the title acid as an off-white solid with a purity of 99.5%.

1. filtrationfiltered
2. customto remove the ether by-product 6-[3-(4-Fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxymethyl-3-(4-fluoro-phenyl)-5-methyl-isoxazole
3. washThe first vessel and the transfer lines were rinsed with a mixture of water (50 mL) and ethanol (50 mL)
4. additionThe filtrate was treated at 20-25° C. within one hour with 25% hydrochloric acid (approx. 280 mL) until the pH was <2.0
5. stirringThe resulting suspension was stirred for one hour at room temperature
6. filtrationThe crystals were filtered off
7. washwashed with a mixture of ethanol (200 mL) and water (200 mL)
8. customsubsequently dried at 50° C./<25 mbar until constant weight