تفاعل #169558

معادلة التفاعل

Methyl 2-(4-chlorophenyl)propanoate

THF

KOtBu

acrylate

→

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

المردود 69.0%

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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%).

المصدر