反应详情

To a cooled (-78° C.) solution of 2.1 g of the 3-amino-2-chloro-6-methyl-4-(trifluoromethyl)pyridine in 10 ml of THF was added dropwise over 3 min. 7 ml of lithium diisopropylamine (LDA, 1.5 M in cyclohexane). The mixture was stirred 5 min., and 0.9 g of 2-chloronicotinoyl chloride in 3 ml of THF was added over 1 min. After 5 min. an additional 3 ml of LDA solution was added followed by an additional 0.5 g of the acid chloride in 1 ml of THF. The resulting mixture was stirred 10 min. and then quenched with 100 ml of water. After partitioning with 30 ml of ethyl acetate, the organic phase was extracted with water and the combined aqueous phases extracted with methylene chloride, dried (magnesium sulfate), filtered and evaporated to give the crude product. This was washed with a small amount of ethyl acetate and dried to give 1.3 g of the title compound.

1. additionwas added dropwise over 3 min
2. stirringThe resulting mixture was stirred 10 min.
3. customquenched with 100 ml of water
4. customAfter partitioning with 30 ml of ethyl acetate
5. extractionthe organic phase was extracted with water
6. extractionthe combined aqueous phases extracted with methylene chloride
7. dry with materialdried (magnesium sulfate)
8. filtrationfiltered
9. customevaporated
10. customto give the crude product
11. washThis was washed with a small amount of ethyl acetate
12. customdried