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

HRID 2209414Notes

Reaction equation

HRID 2209414 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][O:19][CH2:20][CH:21]([O:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]/[CH:36]=[CH:37]\[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:22][N+:23](C)([CH3:25])[CH3:24].[Cl-].CN(C)CC(O)CO.CC(C)([O-])C.[K+]>C1(C)C(C)=CC=CC=1>[CH2:28]([O:27][CH:21]([CH2:20][O:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]/[CH:10]=[CH:9]\[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH2:22][N:23]([CH3:25])[CH3:24])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]/[CH:36]=[CH:37]\[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45]

Participants

5

Reactant 3

HCID 790783-(Dimethylamino)-1,2-propanediolHCID 6438350N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammoniumHCID 23665647Potassium tert-butoxide

Product 1

HCID 11181107Dodma

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

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.

Workup

  1. temperaturewas heated to 50° C.
  2. stirringwith stirring for an additional 15 min
  3. customThe reaction vessel was purged with nitrogen
  4. temperaturethe mixture was heated
  5. temperatureto reflux (≈140° C.) for 3 hr
  6. temperatureAfter cooling
  7. additionthe reaction mixture was diluted with hexane (100 ml)
  8. extractionthe resulting solution was extracted with water (twice, 50 ml each)
  9. concentrationThe organic layer was concentrated
  10. customthe residue was chromatographed over silica gel by elution with a mixture of hexane and diethyl ether (1:2)

Sources & evidence

ORD record
ord-3a8b81c6636741acb0eb4b77c04885f5
Source dataset
uspto-grants-1995_10
Patent number
US05455157

Reaction notes

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