Reaction #162415

Reaction equation

tert-butyl pyridin-3-ylcarbamate

tert-butyllithium

1-piperidinecarboxaldehyde

→

desired product

Yield 60.3%

tert-butyl (4-formylpyridin-3-yl)carbamate

Yield 60.3%

Solvents

THF

pentane

Conditions

Workup

1. 1
   workup.ADDITIONUpon completion of the addition
2. 2
   workup.WAITat −20° C. for 1.5 h
3. 3
   Temperaturewas maintained below at −15° C.
4. 4
   workup.STIRRINGto stir at room temperature overnight
5. 5
   TemperatureThe solution was cooled to 0° C.
6. 6
   Otherwas quenched by the addition of 1 M HCl
7. 7
   workup.ADDITIONSolid Na2CO3 was then added
8. 8
   ExtractionThe solution was extracted with ethyl acetate three times
9. 9
   Washthe combined organic solutions were washed with water (3×) and brine
10. 10
    OtherThe organic layer was dried
11. 11
    Filtrationfiltered
12. 12
    Othervolatiles evaporated
13. 13
    OtherThe residue was purified by silica gel chromatography (50% ethyl acetate/hexanes)

Procedure

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.

Source