Methanamine, N-methoxy-, hydrochloride (1:1) → tert-butyl(S)-(1-(3-acetyl-5-chloropyridin-2-yl)-2-methylpropyl)carbamate

Temperature

-20 °C

To a solution of ethyl(S)-2-(1-((tert-butoxycarbonyl)amino)-2-methylpropyl)-5-chloronicotinate (104 mg, 291 μmol) and N,O-dimethylhydroxylamine hydrochloride (45.5 mg, 466 μmol) in THF (1 mL) was added dropwise methylmagnesium bromide (1.4 M in 3:1 toluene:THF, 1.04 mL) at −20° C. The mixture was stirred at −20° C. for 45 min, at which point it was quenched carefully with cold saturated aqueous ammonium chloride (10 mL). The mixture was extracted with EtOAc (20 mL), then the organic phase was washed with brine (10 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluting with 10% EtOAc in hexanes, gradient to 60%) to afford 62.3 mg of tert-butyl(S)-(1-(3-acetyl-5-chloropyridin-2-yl)-2-methylpropyl)carbamate (56% yield). LC-MS tR=1.08 min in 1 min chromatography, MS (ESI) m/z 327.4 [M+H]+.

1. customwas quenched carefully with cold saturated aqueous ammonium chloride (10 mL)
2. extractionThe mixture was extracted with EtOAc (20 mL)
3. washthe organic phase was washed with brine (10 mL)
4. dry with materialdried over anhydrous MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography (eluting with 10% EtOAc in hexanes, gradient to 60%)

ORD record

ord-f8197157fc704f3e8622eb34570f6173

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09266886B2