Reaktion #82863

Reaktionsgleichung

3-(dimethylamino)-1,2-propanediol

potassium tert-butoxide

oleyl p-toluenesulfonate

→

2,3-dioleyloxy-1-(dimethylamino)propane

Lösungsmittel

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeas outlined in reaction Scheme V
2. 2
   Temperaturwas then heated to 50° C.
3. 3
   workup.STIRRINGwith stirring for an additional 15 min
4. 4
   SonstigeThe reaction vessel was purged with nitrogen
5. 5
   Temperaturthe mixture was heated
6. 6
   Temperaturto reflux (approximately 140° C.) for 3 hrs
7. 7
   TemperaturAfter cooling
8. 8
   workup.ADDITIONthe reaction mixture was diluted with hexane (100 ml)
9. 9
   Extraktionthe resulting solution was extracted with water (2×50 ml)
10. 10
    EinengenThe organic layer was concentrated
11. 11
    Sonstigethe residue was chromatographed over silica gel by elution with a mixture of hexanes and ether (1:2)

Vorschrift

DOTMA (N-(1-(2,3,-Dioleyloxy)propyl)-N,N,N-trimethyl-ammonium chloride) was prepared as outlined in reaction Scheme V. A mixture of 3-(dimethylamino)-1,2-propanediol (Aldrich Chemical Co., 1.19 g, 10 mmol), potassium tert-butoxide (3.36 g, 30 mmol) and oleyl p-toluenesulfonate (12.7 g, 30 mmol) in xylenes (50 ml) was stirred at room temperature and reduced pressure (30 Torr) for 30 min, and was then heated to 50° C. with stirring for an additional 15 min. The reaction vessel was purged with nitrogen, and the mixture was heated to reflux (approximately 140° C.) for 3 hrs. After cooling, the reaction mixture was diluted with hexane (100 ml), and the resulting solution was extracted with water (2×50 ml). The organic layer was concentrated, and the residue was chromatographed over silica gel by elution with a mixture of hexanes and ether (1:2) to afford the intermediate 2,3-dioleyloxy-1-(dimethylamino)propane as a colorless oil. Quaternization was carried out by condensation of methyl chloride (50 ml) into a Parr pressure apparatus cooled to -78° C. containing this compound (10 g). The sealed vessel was heated behind a safety shield at 70° C. for 48 h After cooling to 0° C. the reaction vessel was opened, and the excess methyl chloride was allowed to evaporate under a stream of nitrogen in a well-ventilated hood. The crude residue was recrystallized from acetonitrile to afford DOTMA as an off-white solid, mp. 35°-38° C. Full details of the synthesis of DOTMA and analogs will be published elsewhere (Gadek and Felgner, in preparation).

Quelle