Formic Acid → 6-Dimethylamino hexanoic acid methyl ester

Participants

Reaction Steps

[2-Diethoxy-phosphoryloxy)-ethyl]-(5-methoxycarbonyl-pentyl)-dimethylammonium trifluoroacetate. The methyl ester (1.73 g, 10 mmol) was dissolved in dry acetonitrile (15 mL) and K2CO3 (1.38 g, 10 mmol) was added. This suspension was refluxed under nitrogen gas for 36 h. After cooling to room temperature water was added and the pH was adjusted to 2 by adding TFA. The solution was purified by rp HPLC (Supelco Discovery C18, 21.2 mm×15 cm, 5 μm, A: 5% IPA, 95% H2O, 0.1% TFA, B: 90% IPA, 10% H2O, 0.1% TFA, 0 to 15% B over 14 min, tR=11.8 min) and lyophilized to give the TFA salt of the quaternary amine as light yellow oil (1.06 g, 3.0 mmol, 30%). LC-MS (Phenomenex Gemini, C18, 5 μm, 150×3.0 mm, A: 0.1% formic acid in water, B: 0.1% formic acid in acetonitrile, 10-50% B over 10 min) tR=6.4 min (LSD signal), m/z=354.2 for [M+H]+. 1H NMR (CD3OD, 400 MHz) δ=1.41-1.50 (m, 8H, 2×OCH2CH3 and CH2); 1.77 (m, 2H, CH2); 1.90 (m, 2H, CH2); 2.44 (t, 2H, CH2, 3J=7.2 Hz); 3.25 (s, 6H, N(CH3)2); 3.48 (m, 2H, CH2); 3.72 (s, 3H, COOCH3) 3.82 (m, 2H, CH2); 4.26 (dq, 4H, 2×CH2CH3, 3J(H,H)=6.8 Hz, 3J(H,P)=8.0 Hz); 4.58 (brs, 2H, CH2). 13C NMR (CD3OD, 100.5 MHz) δ=16.4 (d, 2×OCH2CH3, 3J=6.1 Hz); 23.3 (CH2); 25.3 (CH2); 26.7 (CH2); 34.4 (CH2); 52.0 (CH3); 52.2 (CH3); 62.1 (d, CH2, 2J=5.3 Hz); 64.8 (CH2); 66.1 (d, CH2, 2J=6.1 Hz); 66.7 (CH2); 175.5 (CO).

Provenance & Evidence