反応 #2446

反応方程式

ethylmagnesium bromide

butyl lithium

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

3-indanyloxy-4-methoxybenzaldehyde

ammonium chloride

→

product

収率 9.0%

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

収率 9.0%

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 was stirred for one hour
5. 5
   温度The reaction mixture was heated
6. 6
   温度at reflux
7. 7
   workup.WAITAfter 48 hours the reaction had reached
8. 8
   温度to cool to room temperature
9. 9
   抽出The resulting mixture was extracted with methylene chloride (3×15 mL)
10. 10
    乾燥the combined extracts were dried over magnesium sulfate
11. 11
    濃縮concentrated
12. 12
    その他to afford the product which
13. 13
    その他was further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide)

実験手順

To an ice bath cooled stirred solution of 1,1,1,3,3,3-hexamethyldisilazane (2.7 mL, 13 mmol) in tetrahydrofuran (5 mL) under nitrogen, was added a hexane solution of butyl lithium (2.5M, 4.8 mL, 12 mmol) via syringe. The ice bath was removed and the solution was stirred for 25 minutes at room temperature. This solution then was added dropwise to an ice bath cooled solution of 3-indanyloxy-4-methoxybenzaldehyde (2.68 g, 10.0 mmol) in tetrahydrofuran (4 mL) and the mixture was stirred for one hour. An ethereal solution of ethylmagnesium bromide (3M, 6.7 mL, 20 mmol) then was added dropwise via syringe. The reaction mixture was heated at reflux and was monitored by HPLC (Waters Nova-Pak/EC 18 column, 3.9×150 mm, 4 micron, 1 mL/min, 240 nm, 40/60, CH3CN/0.1% H3PO4 (aq)). After 48 hours the reaction had reached completion and was allowed to cool to room temperature. The reaction mixture then was slowly poured into a saturated solution of ammonium chloride (80 mL). The resulting mixture was extracted with methylene chloride (3×15 mL) and the combined extracts were dried over magnesium sulfate and concentrated to afford the product which was further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide) to afford 0.27 g (9%) of product as an orange solid.

出典