Réaction #162415

Équation de réaction

tert-butyl pyridin-3-ylcarbamate

tert-butyllithium

1-piperidinecarboxaldehyde

→

desired product

Rendement 60.3%

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

Rendement 60.3%

Solvants

THF

pentane

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONUpon completion of the addition
2. 2
   workup.WAITat −20° C. for 1.5 h
3. 3
   Températurewas maintained below at −15° C.
4. 4
   workup.STIRRINGto stir at room temperature overnight
5. 5
   TempératureThe solution was cooled to 0° C.
6. 6
   Autrewas 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
   Lavagethe combined organic solutions were washed with water (3×) and brine
10. 10
    AutreThe organic layer was dried
11. 11
    Filtrationfiltered
12. 12
    Autrevolatiles evaporated
13. 13
    AutreThe residue was purified by silica gel chromatography (50% ethyl acetate/hexanes)

Mode opératoire

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