Reacción #1991836

Ecuación de reacción

5-methyl-4-piperidino-2-pyridinecarbaldehyde

(1-naphthylmethyl)triphenylphosphonium chloride

hexane

n-butyllithium

→

captioned compound ( 14-A )

Rendimiento 41.0%

(E)-5-methyl-2-[2-(1-naphthyl)-vinyl]-4-piperidinopyridine hydrochloride

Rendimiento 41.0%

captioned compound ( 14-B )

Rendimiento 37.0%

(Z)-5-methyl-2-[2-(1-naphthyl)vinyl]-4-piperidinopyridine hydrochloride

Rendimiento 37.0%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter the addition
2. 2
   Otrothe cooling bath was removed
3. 3
   Temperaturathe temperature was raised to room temperature
4. 4
   workup.STIRRINGThe mixture was further stirred at room temperature for 1 hour
5. 5
   workup.ADDITIONWater (30 ml) was added to the reaction mixture, and tetrahydrofuran
6. 6
   Otrowas evaporated under reduced pressure
7. 7
   ExtracciónThe remaining aqueous layer was extracted with ether
8. 8
   LavadoThe ether layer was washed with a saturated aqueous sodium chloride solution
9. 9
   Secadodried over anhydrous magnesium sulfate
10. 10
    OtroThe solvent was evaporated under reduced pressure
11. 11
    workup.ADDITIONHexane (500 ml) was added to the residue
12. 12
    OtroThe precipitated triphenylphosphine oxide was removed by filtration
13. 13
    Concentraciónthe filtrate was concentrated under reduced pressure
14. 14
    Otroto give a crude
15. 15
    OtroThe crude mixture was purified by silic gel column chromatography (eluted with hexane/ethyl acetate=2/1)
16. 16
    workup.ADDITIONeach treated with an ethanol solution of hydrogen chloride
17. 17
    Otrorecrystallized from methanol/ether

Procedimiento

A suspension of 13.2 g (30.0 mmoles) of (1-naphthylmethyl)triphenylphosphonium chloride in 150 ml of tetrahydrofuran was cooled to about -30° C. in a cooling bath, and under a stream of nitrogen, 23.2 ml of a 1.55M hexane solution of n-butyllithium was added dropwise. The reaction mixture was further stirred at the above temperature for 0.5 hour, and a solution of 6.2 g (30.0 mmoles) of 5-methyl-4-piperidino-2-pyridinecarbaldehyde in 30 ml of tetrahydrofuran was added dropwise. After the addition, the cooling bath was removed, and the temperature was raised to room temperature. The mixture was further stirred at room temperature for 1 hour. Water (30 ml) was added to the reaction mixture, and tetrahydrofuran was evaporated under reduced pressure. The remaining aqueous layer was extracted with ether. The ether layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Hexane (500 ml) was added to the residue. The precipitated triphenylphosphine oxide was removed by filtration, and the filtrate was concentrated under reduced pressure to give a crude mixture of (E)- and (Z)-5-methyl-2-[2-(1-naphthyl)vinyl]-4-piperidinopyridines. The crude mixture was purified by silic gel column chromatography (eluted with hexane/ethyl acetate=2/1). The resulting (E)- and (Z)-isomers were each treated with an ethanol solution of hydrogen chloride, and then recrystallized from methanol/ether to give 4.5 g (yield 41%) of the captioned compound (14-A) and 3.7 g (yield 37%) of the captioned compound (14-B) as crystals.

Fuente