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

HRID 728743Notes

Reaction equation

HRID 728743 reaction equation
[CH3:1][N:2]([CH3:8])[CH2:3][CH:4]([OH:7])[CH2:5][OH:6].C[C:10]([CH3:13])([O-])[CH3:11].[K+].C1(C)C=CC(S(O[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]/[CH:33]=[CH:34]\[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])(=O)=O)=CC=1>>[CH2:42]([O:7][CH:4]([CH2:5][O:6][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]/[CH:31]=[CH:30]\[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:11][CH2:10][CH3:13])[CH2:3][N:2]([CH3:8])[CH3:1])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]/[CH:34]=[CH:33]\[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH3:25]

Participants

4

Reactant 3

HCID 790783-(Dimethylamino)-1,2-propanediolHCID 11258749Oleyl p-toluenesulfonateHCID 23665647Potassium tert-butoxide

Product 1

HCID 11181107Dodma

Procedure

DOTMA (N-(1-(2,3-Dioleyloxy)propyl)-N,N,N-trimethylammoniun chloride) was prepared as outlined in FIG. 1. 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 ) 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 of DOTMA and analogs will be published elsewhere (Gadek and Felgner, in preparation).

Workup

  1. temperaturewas then 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 (approximately 140° C.) for 3 hrs
  6. temperatureAfter cooling
  7. additionthe reaction mixture was diluted with hexane (100 ml)
  8. extractionthe resulting solution was extracted with water (2×50 ml)
  9. concentrationThe organic layer was concentrated
  10. customthe residue was chromatographed over silica gel by elution with a mixture of hexanes and ether (1:2)

Sources & evidence

ORD record
ord-a36f8b8423b347cea718c2c4bcd54b43
Source dataset
uspto-grants-1991_09
Patent number
US05049386

Reaction notes

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