反応 #169558

反応方程式

Methyl 2-(4-chlorophenyl)propanoate

THF

KOtBu

acrylate

→

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

収率 69.0%

反応条件

後処理

1. 1
   温度The solution was cooled to −78° C.
2. 2
   workup.STIRRINGto stir overnight to room temperature to completion by TLC analysis
3. 3
   その他The mixture was then quenched with saturated NH4Cl
4. 4
   その他The THF was removed in vacuo
5. 5
   その他to afford a yellow oil
6. 6
   その他The residue was partitioned between ethyl acetate and water
7. 7
   抽出The aqueous was extracted with ethyl acetate
8. 8
   洗浄The organic portion was washed with water
9. 9
   その他brine, separated
10. 10
    乾燥dried over MgSO4
11. 11
    ろ過filtered
12. 12
    濃縮concentrated in vacuo
13. 13
    その他to afford the crude material as a yellow oil
14. 14
    その他The material was purified by chromatography (silica gel eluted with 90:10 hexanes:ethyl acetate, Rf=0.35)

実験手順

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%).

出典