Dimethylformamide → tert-Butyl 4-chloro-3-formylpyridin-2-ylcarbamate

Temperature

-78 °C

To a stirred solution of tert-butyl(4-chloropyridin-2-yl)carbamate (1.00 g, 4.37 mmol) in THF (30 mL) cooled to −78° C. was added n-butyllithium (2.55 M in hexane, 4.1 mL, 10.06 mmol) dropwise. After complete addition the solution was stirred at −78° C. for 1 h. DMF (1.591 mL, 20.55 mmol) was added dropwise and the resultant solution stirred at −78° C. for an additional 1 h. The reaction mixture was then quenched by addition of saturated aqueous ammonium chloride solution (20 mL) and extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with brine (1×20 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified via neutral alumina gel chromatography (ethyl acetate/hexanes) to yield tert-butyl(4-chloro-3-formylpyridin-2-yl)carbamate (530 mg, 2.07 mmol, 27% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 10.73 (s, 1H), 10.55 (s, 1H), 8.52 (d, J=5.3 Hz, 1H), 7.06 (d, J=5.3 Hz, 1H), 1.56 (s, 9H); LCMS (ESI) m/e 255.2 [(M−H)−, calcd for C11H12ClN2O3 255.0]; LCMS retention time (Method C): tR=1.73 min.

1. additionAfter complete addition the solution
2. customThe reaction mixture was then quenched by addition of saturated aqueous ammonium chloride solution (20 mL)
3. extractionextracted with ethyl acetate (2×25 mL)
4. washThe combined organic extracts were washed with brine (1×20 mL)
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe crude residue was purified via neutral alumina gel chromatography (ethyl acetate/hexanes)

ORD record

ord-75792d4d1540464385987ab8249691ce

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703953B2