3-(Dimethylamino)-1,2-propanediol → Dodma

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).

1. customas outlined in reaction Scheme V
2. temperaturewas then heated to 50° C.
3. stirringwith stirring for an additional 15 min
4. customThe reaction vessel was purged with nitrogen
5. temperaturethe mixture was heated
6. temperatureto reflux (approximately 140° C.) for 3 hrs
7. temperatureAfter cooling
8. additionthe reaction mixture was diluted with hexane (100 ml)
9. extractionthe resulting solution was extracted with water (2×50 ml)
10. concentrationThe organic layer was concentrated
11. customthe residue was chromatographed over silica gel by elution with a mixture of hexanes and ether (1:2)

ORD-Eintrag

ord-5c28f0f8e59c4212bef2279acd8e08de

Quelldatensatz

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05622712