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

Participants

Reaction Steps

DOTMA may be prepared according to the following protocol: A mixture of 3-(dimethylamino)-l,2-propanediol (Aldrich; 1.19 g, 10 mmol), potassium tert-butoxide (3.36 g, 30 mmol), and oleyl ptoluenesulfonate (12.7 g, 30 mmol) in xylene (50 ml) was stirred at room temperature and reduced pressure (30 torr; 1 torr=133 Pa) for 30 min and then was 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 (≈140° C.) for 3 hr. After cooling, the reaction mixture was diluted with hexane (100 ml), and the resulting solution was extracted with water (twice, 50 ml each). The organic layer was concentrated, and the residue was chromatographed over silica gel by elution with a mixture of hexane and diethyl ether (1:2) to afford the intermediate 2,3-dioleyloxyl(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. and containing this compound (10 g). The sealed vessel was heated behind a safety shield at 70° C. for 48 hr. 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°-58° C.

Provenance & Evidence