反応 #2445

反応方程式

ethylmagnesium bromide

butyl lithium

1,1,1,3,3,3-hexamethyldisilazane

3-cyclopentoxy-4-methoxybenzaldehyde

ammonium chloride

→

product

1-(3-Cyclopentoxy-4-methoxyphenyl)propylamine

溶媒

CH3CN

hexane

tetrahydrofuran

tetrahydrofuran

反応条件

後処理

1. 1
   温度To an ice bath cooled
2. 2
   その他The ice bath was removed
3. 3
   workup.ADDITIONThis solution then was added dropwise to an ice bath
4. 4
   workup.STIRRINGthe mixture stirred for 20 minutes
5. 5
   その他to reach room temperature
6. 6
   workup.STIRRINGwas stirred at room temperature
7. 7
   抽出The resulting mixture was extracted with methylene chloride (3×20 mL)
8. 8
   乾燥the combined extracts were dried over magnesium sulfate
9. 9
   濃縮concentrated in vacuo

実験手順

To an ice bath cooled stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (2.5M, 4.1 mL, 19.5 mmol) in tetrahydrofuran (5 mL) under nitrogen, was added a hexane solution of butyl lithium (7.2 mL, 18 mmol) via syringe. The ice bath was removed and the solution was stirred for 30 minutes at room temperature. This solution then was added dropwise to an ice bath cooled solution of 3-cyclopentoxy-4-methoxybenzaldehyde (3.3 g, 15 mmol) in tetrahydrofuran (5 mL) and the mixture stirred for 20 minutes. An ethereal solution of ethylmagnesium bromide (3M, 10 mL, 30 mmol) then was added dropwise. The reaction solution was allowed to reach room temperature and then was stirred at room temperature. The reaction progress was monitored by HPLC (Waters Nova-Pak/EC 18 column, 3.9×150 mm, 4 micron, 1 mL/min, 240 nm, 35/65, CH3CN/0.1% H3PO4 (aq)) and after 3 hours no starting material remained. The reaction mixture was slowly poured into a saturated solution of ammonium chloride (100 mL). The resulting mixture was extracted with methylene chloride (3×20 mL) and the combined extracts were dried over magnesium sulfate and concentrated in vacuo to yield 5.6 g of product which was further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide) to afford 2.5 g (67%) of the product as an oil: 1H NMR (CDCl3) δ 6.91-6.77 (m, 3H), 4.85-4.74 (m, 1H), 3.83 (s, 3H), 3.74 (t, J=6.8 Hz, 1H), 2.02-1.15 (m, 12H), 0.86 (t, J=7.4 Hz, 3H); 13C NMR (CDCl3) δ 148.8, 147.5, 138.8, 118.4, 113.3, 111.8, 80.3, 57.4, 56.0, 32.7, 32.4, 10.9.

出典