Reaktion #169558

Reaktionsgleichung

Methyl 2-(4-chlorophenyl)propanoate

THF

KOtBu

acrylate

→

5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate

Ausbeute 69.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe solution was cooled to −78° C.
2. 2
   workup.STIRRINGto stir overnight to room temperature to completion by TLC analysis
3. 3
   SonstigeThe mixture was then quenched with saturated NH4Cl
4. 4
   SonstigeThe THF was removed in vacuo
5. 5
   Sonstigeto afford a yellow oil
6. 6
   SonstigeThe residue was partitioned between ethyl acetate and water
7. 7
   ExtraktionThe aqueous was extracted with ethyl acetate
8. 8
   WaschenThe organic portion was washed with water
9. 9
   Sonstigebrine, separated
10. 10
    Trocknendried over MgSO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated in vacuo
13. 13
    Sonstigeto afford the crude material as a yellow oil
14. 14
    SonstigeThe material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35)

Vorschrift

Methyl 2-(4-chlorophenyl)propanoate (1.50 g, 7.55 mmol) was dissolved in THF (14 mL) and cooled to 0° C. The solution was treated with KOtBu (85 mg, 0.755 mmol) and allowed to stir for 15 minutes. The solution was cooled to −78° C. and then treated with the acrylate (1.22 mL, 8.31 mmol). The mixture was allowed to stir overnight to room temperature to completion by TLC analysis. The mixture was then quenched with saturated NH4Cl. The THF was removed in vacuo to afford a yellow oil. The residue was partitioned between ethyl acetate and water. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic portion was washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford the crude material as a yellow oil. The material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35) to afford 5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate as a colorless oil (1.69 g, 69%). This 5-tert-butyl 1-methyl 2-(4-chlorophenyl)-2-methylpentanedioate (1.69 g, 5.17 mmol) was dissolved in TFA (15.9 mL; 207 mmol) at room temperature and allowed to stir for 2 hours to completion by LCMS (neg) analysis. The solution was concentrated in vacuo to afford 4-(4-chlorophenyl)-5-methoxy-4-methyl-5-oxopentanoic acid as a colorless oil (1.42 g, 100%).

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