Reaction #452438

Reaction equation

p-anisoyl chloride

3,7-dimethyl-1,6-octadien-3-yl acetate

Lithium diisopropylamide

→

desired product

3,7-dimethyl-1,6-octadien-3-yl 3-(4-methoxyphenyl)-3-oxo-propionate

Solvents

THF

THF

Conditions

Workup

1. 1
   Otherfitted with a magnetic stirrer
2. 2
   workup.ADDITIONinternal thermometer, argon inlet, and addition funnel
3. 3
   workup.ADDITIONthe resulting solution added to the flask over 45 min
4. 4
   workup.ADDITIONOnce addition
5. 5
   TemperatureThe mixture is warmed to -20° C.
6. 6
   workup.STIRRINGstirred at that temperature for 18 h
7. 7
   TemperatureAfter warming to 0° C.
8. 8
   Otherthe mixture is quenched with 20% HCl (80 mL)
9. 9
   workup.ADDITIONThe mixture is poured into a separatory funnel
10. 10
    workup.ADDITIONcontaining ether (150 mL) and water (250 mL)
11. 11
    ExtractionThe aqueous layer is extracted with ether (50 mL)
12. 12
    workup.ADDITIONThe mixture is poured into a separatory funnel
13. 13
    workup.ADDITIONcontaining ether (150 mL) and water (250 mL)
14. 14
    ExtractionThe aqueous layer is extracted with ether (150 mL)
15. 15
    WashThe combined organic layers are washed with saturated NaHCO3 solution (2×100 mL), water (2×150 mL) and brine (150 mL)
16. 16
    Dryingdried over MgSO4
17. 17
    Filtrationfiltered
18. 18
    OtherThe solvent is removed by rotary evaporation
19. 19
    Otherto give an oil
20. 20
    OtherThe oil is purified by column chromatography (elution with 2% ethyl acetate/petroleum ether)
21. 21
    Otherto yield a colorless oil

Procedure

Lithium diisopropylamide (119.0 mL of a 2.0 M solution, 0.238 mol) is placed into a 500 mL three-necked round-bottomed flask fitted with a magnetic stirrer, internal thermometer, argon inlet, and addition funnel. The flask is cooled to -78° C. 3,7-dimethyl-1,6-octadien-3-yl acetate (22.04 g, 0.112 mol) is dissolved in THF (5 mL) and the resulting solution added to the flask over 45 min. Once addition is complete, the mixture is stirred for an additional 15 min. before being treated with a solution p-anisoyl chloride (35.00 g, 0.106 mol) dissolved in THF (30 mL) over 30 min. The mixture is warmed to -20° C. and stirred at that temperature for 18 h. After warming to 0° C., the mixture is quenched with 20% HCl (80 mL). The mixture is poured into a separatory funnel containing ether (150 mL) and water (250 mL). The aqueous layer is extracted with ether (50 mL). The mixture is poured into a separatory funnel containing ether (150 mL) and water (250 mL). The aqueous layer is extracted with ether (150 mL). The combined organic layers are washed with saturated NaHCO3 solution (2×100 mL), water (2×150 mL) and brine (150 mL), dried over MgSO4 and filtered. The solvent is removed by rotary evaporation to give an oil. The oil is purified by column chromatography (elution with 2% ethyl acetate/petroleum ether) to yield a colorless oil having 1H and 13C NMR spectra consistent with the desired product.

Source