Реакция #162415

Уравнение реакции

tert-butyl pyridin-3-ylcarbamate

tert-butyllithium

1-piperidinecarboxaldehyde

→

desired product

Выход 60.3%

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

Выход 60.3%

Растворители

THF

pentane

Условия реакции

Обработка

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

Методика

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.

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