Reacción #1579199

Ecuación de reacción

δ-valerolactone

t-butyldimethylsilyloxyacetaldehyde

lithium diisopropylamide

3-lithiopyridine

3-bromopyridine

n-butyllithium

n-butyllithium

diisopropyl amine

→

1-(t-butyldimethylsilyloxy)-3-nicotinoylhexan-2,6-diol

Disolventes

ether

ether

hexane

ether

ether

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONby adding at 0° C
2. 2
   workup.STIRRINGthe mixture is stirred at -78° C. for 40 min
3. 3
   Otroprepared
4. 4
   workup.STIRRINGstirring the mixture for 1/2 h
5. 5
   workup.STIRRINGThe mixture is stirred at -78° C. for 1 h
6. 6
   Otroquenched with 20 ml of concentrated aqueous ammonium chloride
7. 7
   TemperaturaThe mixture is warmed to 10° C.
8. 8
   Lavadowashed with 10 ml of water and brine
9. 9
   Secadodried (MgSO4)
10. 10
    Otroevaporated
11. 11
    OtroThe residue is purified by flash chromatography

Procedimiento

To a solution of lithium diisopropylamide prepared by adding at 0° C. 6.1 ml (0.0122 mole) of 2.01 molar solution of n-butyllithium to a stirring solution of 1.23 g (0.0122 mole) of diisopropyl amine in 25 ml of ether and cooling the solution to -78° C., a solution of 1.2 g (0.0122 mole) of δ-valerolactone in 2 ml of ether is added dropwise over a period of 5 min. The mixture is stirred at -78° C. for 1 h and a solution of 2.12 g (0.0122 mole) of t-butyldimethylsilyloxyacetaldehyde in 2 ml of ether is added dropwise and the mixture is stirred at -78° C. for 40 min. The resulting solution, is transferred via a glass cannula into a stirred suspension of 3-lithiopyridine prepared by adding dropwise 1.56 g (0.0162 mole) of 3-bromopyridine into a solution of 7.4 ml (0.0149mole) of 2.01 molar solution of n-butyllithium in hexane in 60 ml of ether at -78° C. and stirring the mixture for 1/2 h. The mixture is stirred at -78° C. for 1 h and quenched with 20 ml of concentrated aqueous ammonium chloride. The mixture is warmed to 10° C. washed with 10 ml of water and brine, dried (MgSO4) and evaporated. The residue is purified by flash chromatography using methylene chloride-methanol-ammonium hydroxide (300:25:1) as eluent to give 1-(t-butyldimethylsilyloxy)-3-nicotinoylhexan-2,6-diol as an oil.

Fuente