1-Piperidinecarboxaldehyde → Tert-butyl 4-formylpyridin-3-ylcarbamate

Temperature

-78 °C

A solution of tert-butyl pyridin-3-ylcarbamate (17.7 g, 91.1 mmol) in THF (300 mL) was cooled to −78° C. and treated with 1.70 M tert-butyllithium in pentane (129 mL). Upon completion of the addition, the reaction was stirred at −78° C. for an additional 15 min and then at −20° C. for 1.5 h. 1-piperidinecarboxaldehyde (30.4 mL, 0.273 mol) was added while the temperature was maintained below at −15° C., and then the mixture was allowed to stir at room temperature overnight. The solution was cooled to 0° C. and was quenched by the addition of 1 M HCl to bring the pH to 2. Solid Na2CO3 was then added to adjust the pH to 7. The solution was extracted with ethyl acetate three times, and the combined organic solutions were washed with water (3×) and brine. The organic layer was dried, filtered, and volatiles evaporated. The residue was purified by silica gel chromatography (50% ethyl acetate/hexanes) to give the desired product as a yellow solid (12.2 g, 60%). LCMS for C11H15N2O3(M+H)+: m/z=223.1.

1. additionUpon completion of the addition
2. waitat −20° C. for 1.5 h
3. temperaturewas maintained below at −15° C.
4. stirringto stir at room temperature overnight
5. temperatureThe solution was cooled to 0° C.
6. customwas quenched by the addition of 1 M HCl
7. additionSolid Na2CO3 was then added
8. extractionThe solution was extracted with ethyl acetate three times
9. washthe combined organic solutions were washed with water (3×) and brine
10. customThe organic layer was dried
11. filtrationfiltered
12. customvolatiles evaporated
13. customThe residue was purified by silica gel chromatography (50% ethyl acetate/hexanes)

ORD record

ord-a7af190c10b84e4a9ea49a32115a1280

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08835423B2