Ammonium Chloride → (R)-3-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-2,2-difluoro-3-((R)-2-methyl-propane-2-sulfinylamino)-butyric acid ethyl ester

To a suspension of zinc (466 mg, 7.12 mmol) and copper(I) chloride (34 mg, 0.344 mmol) in dry THF (20 ml) were added 3 drops of trimethylchlorosilane under nitrogen to activate the zinc. After 10 minutes ethyl 2-bromo-2,2-difluoroacetate (1.398 g, 6.89 mmol) was added slowly by syringe over a period of 10 minutes at 25° C. (slightly exothermic). The reaction mixture was kept in an ultrasound bath for 45 minutes. This black fine suspension was added dropwise to a solution of (R)-2-methyl-propane-2-sulfinic acid [1-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-eth-(E)-ylidene]-amide) (1 g, 2.296 mmol) in dry THF (10 ml) at it under inert atmosphere. After 4 h at it the reaction mixture was added to a cold aq. ammonium chloride solution (5%) and was diluted with ethyl acetate. The organic phase was washed with aq. citric acid (5% solution), water, sat. sodium bicarbonate solution and brine, dried over sodium sulfate, filtered and concentrated. The crude brownish oil (1.5 g) was chromatographed over silica gel (cyclohexane/ethyl acetate 83:17) to give the title compound as a light yellow oil. 984 mg (77% yield).

1. washThe organic phase was washed with aq. citric acid (5% solution), water, sat. sodium bicarbonate solution and brine
2. dry with materialdried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. customThe crude brownish oil (1.5 g) was chromatographed over silica gel (cyclohexane/ethyl acetate 83:17)

ORDレコード

ord-6de3b259cf004013b8fb25f07fff9a97

出典データセット

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09163011B2