반응 #425552

반응 방정식

cyclobutanone

2-bromo-5-iodoanisole

n-butyl lithium

→

title compound

수율 12.2%

1-(4-Bromo-3-methoxy-phenyl)cyclobutanol

수율 12.2%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.STIRRINGstirred at −78° C. for an additional 1.5 hours
2. 2
   기타The reaction was quenched with saturated aqueous ammonium chloride solution
3. 3
   온도warmed to room temperature
4. 4
   추출extracted with ethyl acetate (2×)
5. 5
   건조The combined organic layers were dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   농축concentrated in vacuo
8. 8
   기타to afford a yellow oil, which
9. 9
   기타was purified by flash chromatography (12 g silica, 0-50% ethyl acetate/heptane, 27 column volumes)
10. 10
    농축concentrated in vacuo

실험 절차

To a solution of 2-bromo-5-iodoanisole (400 mg, 1.28 mmol) in tetrahydrofuran (5 mL) at −78° C. was added n-butyl lithium (2.5M in hexane, 0.62 mL, 1.55 mmol) dropwise over 15 minutes. The reaction mixture was stirred at −78° C. for 30 minutes, then treated with neat cyclobutanone (0.1 mL, 1.3 mmol) dropwise over 10 minutes and stirred at −78° C. for an additional 1.5 hours. The reaction was quenched with saturated aqueous ammonium chloride solution, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford a yellow oil, which was purified by flash chromatography (12 g silica, 0-50% ethyl acetate/heptane, 27 column volumes). Product fractions were combined and concentrated in vacuo to afford the title compound as a pale yellow oil (40 mg, 12% yield). GCMS 256/258 (M)+; 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J=8.29 Hz, 1H), 7.09 (d, J=1.95 Hz, 1H), 6.98 (dd, J=8.17, 1.83 Hz, 1H), 3.94 (s, 3H), 2.51-2.61 (m, 2H), 2.35-2.46 (m, 2H), 2.02-2.10 (m, 1H), 1.66-1.79 (m, 1H).

출처