Reaktion #2446

Reaktionsgleichung

ethylmagnesium bromide

butyl lithium

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

3-indanyloxy-4-methoxybenzaldehyde

ammonium chloride

→

product

Ausbeute 9.0%

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

Ausbeute 9.0%

Lösungsmittel

CH3CN

hexane

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturTo an ice bath cooled
2. 2
   SonstigeThe 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
   TemperaturThe reaction mixture was heated
6. 6
   Temperaturat reflux
7. 7
   workup.WAITAfter 48 hours the reaction had reached
8. 8
   Temperaturto cool to room temperature
9. 9
   ExtraktionThe resulting mixture was extracted with methylene chloride (3×15 mL)
10. 10
    Trocknenthe combined extracts were dried over magnesium sulfate
11. 11
    Einengenconcentrated
12. 12
    Sonstigeto afford the product which
13. 13
    Sonstigewas further purified by flash column chromatography (silica gel, 250/10/1, methylene chloride/methanol/ammonium hydroxide)

Vorschrift

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.

Quelle