반응 #41972

반응 방정식

3-chloro-1-propanol

sodium hydride

3-fluorophenol

→

title compound

수율 78.3%

3-(3-Fluorophenoxy)-propan-ol

수율 78.3%

용매

dimethylformamide

water

dimethylformamide

반응 조건

후처리

1. 1
   기타To a pre-dried round bottom flask, equipped with a magnetic stirrer
2. 2
   세척Wash the sodium hydride with hexanes (3×100 mL)
3. 3
   기타to remove the mineral oil
4. 4
   workup.ADDITIONdimethylformamide (165 mL) is added
5. 5
   기타resulting in gas evolution
6. 6
   기타is recooled to 0° C.
7. 7
   기타The resulting reaction mixture
8. 8
   온도is heated to 60° C. for 2.5 h
9. 9
   온도The solution is cooled
10. 10
    기타the dimethylformamide is removed under reduced pressure
11. 11
    기타the resulting reaction mixture
12. 12
    추출extracted with diethyl ether (3×150 mL)
13. 13
    세척The combined organic extracts are washed with water (200 mL), 2 M aqueous sodium hydroxide (200 mL), water (200 mL) and brine (200 mL)
14. 14
    건조The organic layer is dried over magnesium sulfate
15. 15
    여과filtered
16. 16
    농축concentrated

실험 절차

To a pre-dried round bottom flask, equipped with a magnetic stirrer, add sodium hydride (60% dispersion in mineral oil, 4.80 g, 0.120 mol) under a nitrogen atmosphere. Wash the sodium hydride with hexanes (3×100 mL) to remove the mineral oil then dimethylformamide (165 mL) is added. The resulting suspension is cooled to 0° C. and a solution of 3-fluorophenol (11.20 g, 0.100 mol) in dimethylformamide (35 mL) is added dropwise resulting in gas evolution and a color change from green to blue-green. After stirring the reaction mixture at rt for approximately 30 min the reaction is recooled to 0° C. and a solution of 3-chloro-1-propanol (9.46 g, 0.100 mol) in dimethylformamide (35 mL) is added dropwise. The resulting reaction mixture is heated to 60° C. for 2.5 h. The solution is cooled, the dimethylformamide is removed under reduced pressure and the resulting reaction mixture is diluted with water (250 mL) and extracted with diethyl ether (3×150 mL). The combined organic extracts are washed with water (200 mL), 2 M aqueous sodium hydroxide (200 mL), water (200 mL) and brine (200 mL). The organic layer is dried over magnesium sulfate, filtered and concentrated to afford the slightly impure title compound (13.32 g, 78%) as an amber oil which is used directly in the next reaction without purification: Rf 0.40 (19:1 CH2Cl2/MeOH); 1H NMR (300 MHz; CDCl3), δ 1.68 (t, J=5.1 Hz, 1H), 2.04 (quintuplet, J=6.0 Hz, 2H), 3.83-3.89 (m, 2H), 4.10 (t, J=6.0 Hz, 2H), 6.59-6.70 (m, 3H), 7.17-7.25 (m, 1H); 19FNMR (282 MHz, CDCl3), δ-112.13; APCI MS m/z 153 [C9H11FO2+H—H2O]+.

출처