反応 #41972

反応方程式

3-chloro-1-propanol

sodium hydride

3-fluorophenol

→

title compound

収率 78.3%

3-(3-Fluorophenoxy)-propan-ol

収率 78.3%

溶媒

dimethylformamide

water

dimethylformamide

反応条件

後処理

1. 1
   その他To a pre-dried round bottom flask, equipped with a magnetic stirrer
2. 2
   洗浄Wash the sodium hydride with hexanes (3×100 mL)
3. 3
   その他to remove the mineral oil
4. 4
   workup.ADDITIONdimethylformamide (165 mL) is added
5. 5
   その他resulting in gas evolution
6. 6
   その他is recooled to 0° C.
7. 7
   その他The resulting reaction mixture
8. 8
   温度is heated to 60° C. for 2.5 h
9. 9
   温度The solution is cooled
10. 10
    その他the dimethylformamide is removed under reduced pressure
11. 11
    その他the resulting reaction mixture
12. 12
    抽出extracted with diethyl ether (3×150 mL)
13. 13
    洗浄The 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
    乾燥The organic layer is dried over magnesium sulfate
15. 15
    ろ過filtered
16. 16
    濃縮concentrated

実験手順

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]+.

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