反应详情

温度

35 °C

To a suspension of 1-(4-fluorophenyl)-2-(5-trifluoromethyl-2-pyridinyl)ethanone oxime (189 g, 630 mmol) in DME (700 ml) at −3° C. was added methanesulfonyl chloride (50.5 ml, 650 mmol) and the mixture stirred for 15 minutes. Triethylamine (182 ml, 1.31 mol) in DME (74 ml) was then added dropwise over 15 min. After the addition was complete, the reaction was then warmed to 35° C. for 45 minutes. It was then cooled and filtered, washing with DME (180 ml). To the filtrate was added iron (II) chloride (0.87 g) and the mixture was then heated to 75° C. for 2.5 hour then allowed to cool. Water (700 ml) was added, the resulting solid removed by filtration, washed with water and dried. This solid was dissolved in dichloromethane (1.5 l) and purified in two portions by Biotage chromatography eluting with hexane-ethyl acetate (3:1). Combination and concentration of the appropriate fractions gave 148.3 g (84%) of the title compound.

1. additionAfter the addition
2. temperatureIt was then cooled
3. filtrationfiltered
4. washwashing with DME (180 ml)
5. additionTo the filtrate was added iron (II) chloride (0.87 g)
6. temperaturethe mixture was then heated to 75° C. for 2.5 hour
7. temperatureto cool
8. additionWater (700 ml) was added
9. customthe resulting solid removed by filtration
10. washwashed with water
11. customdried
12. dissolutionThis solid was dissolved in dichloromethane (1.5 l)
13. custompurified in two portions by Biotage chromatography
14. washeluting with hexane-ethyl acetate (3:1)