反应详情

温度

24 °C

To a clean and dry nitrogen purged 22 L round bottom flask under nitrogen atmosphere was charged: 500 g of 5-(methylsulfonyl)-2-hydrazinyl-pyridine (2.67 moles), 10 L water (20 volumes) and 579 mL of concentrated H2SO4 (0.063 volumes). In a separate 12 L 3-neck round-bottomed flask was prepared a solution of 7500 mL of isopropanol (15 volumes) and 508 g (2.56 moles) of 4,4-difluoro-1-phenyl-1,3-butanedione. The isopropanol/4,4-difluoro-1-phenyl-1,3-butanedione solution was added to the mixture containing the 5-(methylsulfonyl)-2-hydrazinyl-pyridine, keeping the pot temperature below 30° C. After addition of the 4,4-difluoro-1-phenyl-1,3-butanedione solution, the mixture was stirred at 24° C. for 1.0 hour and sampled for disappearance of 5-(methylsulfonyl)-2-hydrazinyl-pyridine by HPLC. The pot was then heated to 40° C. for 2 hours until disappearance of the intermediate compound of formula 4 and the resulting slurry was filtered and washed with water to achieve a pH of the filtrate of from about 6-7. The solids were then charged to a 5L 3-neck round-bottom flask. To the flask was added 1250 mL water (2.5 volumes) and 1250 mL isopropanol (2.5 volumes). The mixture was heated to reflux (85° C.) for 2 hours. The pot was then cooled to 40° C. and then stirred overnight. The solids were isolated by filtration, washed with 2 L isopropanol, and dried in a vacuum oven at 45° C. The compound of formula 6 was present at a level of 1.2% 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. customTo a clean and dry nitrogen purged 22 L round bottom flask under nitrogen atmosphere
2. additionwas charged
3. customthe pot temperature below 30° C
4. filtrationthe resulting slurry was filtered
5. washwashed with water
6. additionThe solids were then charged to a 5L 3-neck round-bottom flask
7. additionTo the flask was added 1250 mL water (2.5 volumes) and 1250 mL isopropanol (2.5 volumes)
8. temperatureThe mixture was heated
9. temperatureto reflux (85° C.) for 2 hours
10. temperatureThe pot was then cooled to 40° C.
11. stirringstirred overnight
12. customThe solids were isolated by filtration
13. washwashed with 2 L isopropanol
14. customdried in a vacuum oven at 45° C
15. customHPLC retention time (title compound) 8.4 minutes