Ethyl difluoroacetate → 1-(6-Bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2,2-difluoroethanone

To a freshly prepared solution of LDA (6.25 mmol) in THF (5 ml) was added dropwise a solution of 2-bromo-5-fluoro-4-triethylsilanylpyridine (1.6 g, 5.51 mmol) in THF (12 ml) at −78° C. Stirring was continued at −78° C. for 3 hours. Ethyl 2,2-difluoroacetate (0.58 ml, 5.51 mmol) was added dropwise and the solution was stirred at −78° C. for 3 hours. The reaction mixture was quenched with sat. ammonium chloride solution (20 ml) and ethyl acetate was added. The organic phase was washed with brine, dried over sodium sulfate, filtered and evaporated. The crude brown oil (2.11 g) was chromatographed over silica gel (cyclohexane/ethyl acetate) to give the title compound. 1.53 g (75% yield, mixture of ketone and hydrate form).

1. stirringthe solution was stirred at −78° C. for 3 hours
2. customThe reaction mixture was quenched with sat. ammonium chloride solution (20 ml) and ethyl acetate
3. additionwas added
4. washThe organic phase was washed with brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. customevaporated
8. customThe crude brown oil (2.11 g) was chromatographed over silica gel (cyclohexane/ethyl acetate)

ORDレコード

ord-8b80c22b8d764aa592c7574f6d298588

出典データセット

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08865712B2