Synthesis of the cationic lipid 2,3-di(tetradecyloxy)propan-1-amine 3
a
1
b
2
3
Reagents and Conditions a. C 14H29Br, Bu 4NHSO4, 50%NaOH:Toluene, 65 ºC, overnight; b. i. DCM:TFA (10%), 30 min, r.t.;
ii. IRA 900 NaCO3 - form, AcOEt, 1h, r.t.
N-Boc protected diol 1 (500 mg; 2.62 mmol) and 1-bromotetradecane (10 eq) were suspended
in 3.0 mL of anhydrous toluene. Then, Bu4NHSO4 was added along with 3.0 mL of aqueous 50%
NaOH solution. The mixture was heated at 65 ºC and vigorously stirred overnight. Organic
layer was extracted by adding more toluene (10 mL) and washing with water (3 x 10 mL),
Organic layer was dried (anhydrous MgSO4) and the solvent was evaporated until it dried. The
crude was purify by flash chromatography (Hexane 100% to Hex:AcOEt 10%) achieving the
Boc-protected amine dialkyl compound 2 in 45% of yield. 2 was dissolved in a mixture of
dichloromethane:trifluoroacetic acid (10%) and was stirred at room temperature for 30
minutes. The solvent was evaporated and the crude was subsequently dissolved in AcOEt (10
mL). Then, IRA® 900 NaCO3- form was added (20 eq) and mixture was stirred two hours at
room temperature. The resin was filtered off and the solvent was evaporated yielding the
expected free amine 3 in quantitative form.
2,3-di(tetradecyloxy)propan-1-amine (3)
1
H-RMN (400 MHz; CDCl3) δ 3.63 (dd, J = 2.3 Hz, 6.2 Hz; 1H), 3.43 (m, 5H), 3.35 (m,
1H), 2.89 (dd, J = 1.62 Hz, 6.1 Hz; 1H), 2.75 (dd, J = 1.57 Hz, 6.3 Hz; 1H), 1.60 (m,
4H), 1.27 (m, 42H), 0.87 (t, J = 7.2 Hz, 6H)