반응 #57105

반응 방정식

Cyclopentyl bromide

n-butyllithium

diisopropylamine

3-chlorophenylacetic acid

→

(3-chlorophenyl)(cyclohexyl)acetic acid

수율 79.0%

용매

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   온도The solution was re-cooled to −78° C.
2. 2
   온도to warm to 25° C. where it
3. 3
   workup.STIRRINGwas stirred for 45 minutes
4. 4
   온도was then re-cooled to −78° C
5. 5
   workup.STIRRINGthe resulting mixture was stirred at −78° C. for 1 hour
6. 6
   온도to warm to room temperature
7. 7
   workup.STIRRINGstirred overnight
8. 8
   기타The reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride
9. 9
   기타the tetrahydrofuran was removed in vacuo
10. 10
    workup.DISSOLUTIONThe resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL)
11. 11
    세척washed with ethyl acetate (1×15 mL)
12. 12
    workup.ADDITIONThe aqueous layer was then acidified to pH=1 with the addition of a 2 N aqueous solution of hydrochloric acid
13. 13
    추출The product was extracted with ethyl acetate (3×15 mL)
14. 14
    건조the combined organic extracts were dried over magnesium sulfate
15. 15
    농축concentrated in vacuo
16. 16
    기타the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% EtOAc/hexane to 40% EtOAc/hexane)

실험 절차

A solution of diisopropylamine (1.80 mL, 12.9 mmol) in dry tetrahydrofuran (6 mL) under nitrogen was cooled to −78° C. and treated dropwise with a solution of n-butyllithium (2.4 M in hexanes, 5.4 mL, 12.9 mmol). The resulting solution was warmed to 0° C. and stirred for 15 min. The solution was re-cooled to −78° C. and treated, via cannula, with a solution of 3-chlorophenylacetic acid (1.0 g, 5.9 mmol) in tetrahydrofuran (6 mL). The reaction was then allowed to warm to 25° C. where it was stirred for 45 minutes and was then re-cooled to −78° C. Cyclopentyl bromide (0.76 mL, 7.1 mmol) was then added via syringe, and the resulting mixture was stirred at −78° C. for 1 hour. The reaction mixture was allowed to warm to room temperature and then stirred overnight. The reaction was then quenched by the addition of a saturated aqueous solution of ammonium chloride, and the tetrahydrofuran was removed in vacuo. The resulting residue was dissolved in a 2N aqueous solution of sodium hydroxide (30 mL) and washed with ethyl acetate (1×15 mL). The aqueous layer was then acidified to pH=1 with the addition of a 2 N aqueous solution of hydrochloric acid. The product was extracted with ethyl acetate (3×15 mL), and the combined organic extracts were dried over magnesium sulfate, concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% EtOAc/hexane to 40% EtOAc/hexane) to yield 1.08 g (79%) (3-chlorophenyl)(cyclohexyl)acetic acid as a clear oil. HRMS: calcd for C13H15ClO2−H, 237.06823; found (ESI, [M−H]−), 237.0682

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