反应详情

温度

75 °C

To 12.2 kg of 5-(methylsulfonyl)-2-hydrazinyl-pyridine (64.1 moles) was charged isopropanol (45 gallons) followed by 4,4-difluoro-1-phenyl-1,3-butanedione (12.0 kg, 61.5 moles, 0.96 eq.) as a melt, followed by 45 gallons of isopropanol. The slurry was stirred for 15 minutes, then 3.6 L of concentrated sulfuric acid was added (slight exotherm) (30V of isopropanol total). The reaction was heated to 75° C. and held for 1 hour. The pot was then cooled to 20-30° C. After reaction completion assay, 126 gallons (40V) of water was added (slight exotherm, reaction temp kept below 45° C.) and the reaction product was granulated for 2 hours. The product was filtered on a 36-inch nutche filter dressed with a poly cloth in less than 2 hours. The filter cake was rinsed with an additional 12 gallons (4V) of water, and the cake was blown dry for 12 hours. The product contained 2.2% of compound 6 as the major impurity (by HPLC; retention time 5.1 minutes). Analytical data: HPLC retention time (title compound) 8.4 minutes; MS: 349.36 (calc), M+1=350.1; 1H NMR in CDCl3: 8.75 doublet, (1H), 8.26 Quartet (1H), 7.38 multiplet (3H), 7.36 doublet (2H), 6.70 multiplet (2H), 3.08, Singlet, (3H); 13C NMR in CDCl3: 15.3, 149.3, 147.9, 146.6, 138.1, 130.27, 133.5, 130.0, 129.1, 128.7, 117.9, 113.4, 111.1, 108.1, 107.7, 45.).

1. waitheld for 1 hour
2. temperatureThe pot was then cooled to 20-30° C
3. additionwas added
4. custom(slight exotherm, reaction temp kept below 45° C.)
5. waitthe reaction product was granulated for 2 hours
6. filtrationThe product was filtered on a 36-inch
7. filtrationnutche filter
8. waitdressed with a poly cloth in less than 2 hours
9. washThe filter cake was rinsed with an additional 12 gallons (4V) of water
10. customthe cake was blown dry for 12 hours
11. customHPLC retention time (title compound) 8.4 minutes