Reaction #2075685

Reaction equation

3-Dimethylamino-2-(Cholest-5-en-3β-oxybutan-4-oxy)-1-propanol

Sodium hydride

Linoleyl mesylate

→

colorless oil

Yield 81.0%

3-Dimethylamino-2-(cholest-5-en-3β-oxybutan-4-oxy)-1-(cis,cis-9,12-octadecadienoxy)propane

Yield 81.0%

Solvents

toluene

Conditions

Workup

1. 1
   workup.ADDITIONA stir bar was added to the flask, which
2. 2
   Otherwas then sealed
3. 3
   Otherflushed with argon
4. 4
   workup.ADDITIONcharged with anhydrous toluene (100 mL)
5. 5
   workup.ADDITIONadded slowly to the reaction mixture
6. 6
   OtherThe flask was fitted with a reflux condenser
7. 7
   Otherthe apparatus was flushed with argon
8. 8
   TemperatureThe reaction mixture was heated in an oil bath
9. 9
   workup.STIRRINGto stir
10. 10
    Temperatureat reflux overnight
11. 11
    workup.ADDITIONethanol was added dropwise until gas evolution
12. 12
    workup.ADDITIONThe reaction mixture was diluted with ethyl acetate (300 mL)
13. 13
    Washwashed with aqueous 10% sodium carbonate (2×200 mL)
14. 14
    Extractionback extracted with ethyl acetate (2×100 mL)
15. 15
    Dryingdried over MgSO4
16. 16
    Filtrationfiltered
17. 17
    Concentrationconcentrated
18. 18
    OtherThe resultant oil was purified via column chromatography (10% EtOAc/Hexanes, 3% TEA)

Procedure

3-Dimethylamino-2-(Cholest-5-en-3β-oxybutan-4-oxy)-1-propanol (2.6 g, 4.6 mmol) was weighed into a 200 mL round bottomed flask and co-evaporated with anhydrous toluene 2×20 mL). A stir bar was added to the flask, which was then sealed, flushed with argon and charged with anhydrous toluene (100 mL). Sodium hydride (0.7 g, 6 equiv) was added at once and the mixture was stirred, under argon, for 20 minutes. Linoleyl mesylate (4.6 g, 2.3 equiv.) was measured in a PP syringe and added slowly to the reaction mixture. The flask was fitted with a reflux condenser and the apparatus was flushed with argon. The reaction mixture was heated in an oil bath and allowed to stir at reflux overnight. The reaction mixture was then cooled to room temperature in a water bath and ethanol was added dropwise until gas evolution ceased. The reaction mixture was diluted with ethyl acetate (300 mL) and washed with aqueous 10% sodium carbonate (2×200 mL). The aqueous phases were combined and back extracted with ethyl acetate (2×100 mL). The organic phases were combined, dried over MgSO4, filtered and concentrated. The resultant oil was purified via column chromatography (10% EtOAc/Hexanes, 3% TEA) to afford 3.0 g (81%) of a colorless oil.

Source