Reacción #7924

Ecuación de reacción

5-methoxy-1-indanone

butyraldehyde

diisopropylamine

butyllithium

pentane

→

2-butylidene-5-methoxy-1-indanone

Disolventes

THF

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturacooled in an ice bath
2. 2
   workup.ADDITIONwas added dropwise over 2 minutes
3. 3
   Temperaturacooled in a dry ice-acetone bath
4. 4
   workup.STIRRINGAfter stirring at −78° C. for 20 minutes
5. 5
   workup.STIRRINGAfter stirring an additional 26 minutes at −78° C.
6. 6
   Otrothe reaction mixture was removed from the cooling bath
7. 7
   workup.STIRRINGstirred at room temperature for 90 hours
8. 8
   workup.ADDITIONThe reaction mixture was treated with saturated aqueous NH4Cl solution (10 mL)
9. 9
   Extracciónextracted with EtOAc (15 mL)
10. 10
    LavadoThe organic phase was washed with brine (25 ml)
11. 11
    Secadodried over MgSO4
12. 12
    Filtraciónfiltered
13. 13
    Otroevaporated under vacuum to an oil (353 mg)
14. 14
    OtroThe crude product was purified by silica gel chromatography on a Biotage FLASH 12M column (1.2×15 cm)
15. 15
    Lavadoeluting with 7:1 hexanes-EtOAc

Procedimiento

A solution of diisopropylamine (0.227 mL, 1.62 mmol) in anhydrous tetrahydrofuran (THF, 15 mL) was placed under a nitrogen atmosphere, cooled in an ice bath, and stirred while a 2.0M solution of butyllithium in pentane (0.771 mL, 1.54 mmol) was added dropwise over 2 minutes. The solution was stirred at room temperature for 15 minutes, then cooled in a dry ice-acetone bath and treated dropwise over 3 minutes with a solution of 5-methoxy-1-indanone (250 mg, 1.54 mmol) in THF (2 mL). After stirring at −78° C. for 20 minutes, the reaction mixture was treated with butyraldehyde (0.167 mL, 1.85 mmol). After stirring an additional 26 minutes at −78° C., the reaction mixture was removed from the cooling bath and stirred at room temperature for 90 hours. The reaction mixture was treated with saturated aqueous NH4Cl solution (10 mL) and extracted with EtOAc (15 mL). The organic phase was washed with brine (25 ml), dried over MgSO4, filtered, and evaporated under vacuum to an oil (353 mg). The crude product was purified by silica gel chromatography on a Biotage FLASH 12M column (1.2×15 cm), eluting with 7:1 hexanes-EtOAc, to afford 2-butylidene-5-methoxy-1-indanone (205 mg) as a solid.

Fuente