Реакция #1279522

Уравнение реакции

(4-chlorophenyl)-acetic acid ethyl ester

potassium tert-butoxide

tert-butyl acrylate

→

2-(4-chlorophenyl)-pentanedioic acid 5-tert-butyl ester 1-ethyl ester

Растворители

THF

Условия реакции

Обработка

1. 1
   Температураcooled to −78° C
2. 2
   workup.STIRRINGto stir overnight
3. 3
   Температураwarming slowly to room temperature
4. 4
   КонцентрированиеThe reaction solution was concentrated in vacuo
5. 5
   Другоеthe residue was partitioned between ethyl acetate and saturated NH4Cl solution
6. 6
   ЭкстракцияThe aqueous was extracted with ethyl acetate
7. 7
   ПромывкаThe organic was washed with brine
8. 8
   Другоеseparated
9. 9
   Сушкаdried over MgSO4
10. 10
    Фильтрацияfiltered
11. 11
    Концентрированиеconcentrated in vacuo
12. 12
    ДругоеThe residue was purified by chromatography (silica gel eluted with 9:1 hexanes:EtOAc)

Методика

The (4-chlorophenyl)-acetic acid ethyl ester (9.52 g, 47.9 mmol) was dissolved in 80 mL of THF, cooled to 0° C., and treated with potassium tert-butoxide (538 mg, 4.79 mmol). The resulting orange solution was allowed to stir for 15 minutes at 0° C., then cooled to −78° C. The tert-butyl acrylate (7.72 mL, 52.7 mmol) was added in three equal portions over ten minutes. The solution was allowed to stir overnight warming slowly to room temperature. The reaction solution was concentrated in vacuo, and the residue was partitioned between ethyl acetate and saturated NH4Cl solution. The aqueous was extracted with ethyl acetate, and the organics were combined. The organic was washed with brine, separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by chromatography (silica gel eluted with 9:1 hexanes:EtOAc) to afford the 2-(4-chlorophenyl)-pentanedioic acid 5-tert-butyl ester 1-ethyl ester in greater than 80% purity (9.00 g, 57%). 1H NMR (CDCl3, 400 MHz) δ 7.31-7.21 (m, 4H), 4.13 (q, J=7.6 Hz, 2H), 3.58 (t, J=8.0 Hz, 1H), 2.27 (m, 1H), 2.16 (t, J=7.2 Hz, 2H), 2.04 (m, 1H), 1.43 (s, 9H), 1.21 (t, J=7.6 Hz, 3H).

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