Optimization of reaction conditions for REM resin-bound quaternization reactions.
A study into the effect of reaction variables on the quaternization of REM resin-bound tertiary amines was undertaken. The influence of resin matrix, solvent, reaction time, temperature, and amount of quaternization agent on the outcome of reaction was evaluated by reaction monitoring using (19)F NMR. The highest yields of tertiary amine products were seen when DMSO was used as reaction solvent in conjunction with a reaction time of 18 h at room temperature. The use of heating for extended reaction times tended to depress yields, indicating product cleavage during quaternization. Quaternization on PS-DVB resin was found to be more robust than reaction on PS-PEG matrices where yields were generally considerably lower than the observed conversions. DMSO was the most efficient reaction solvent for both resins despite poor swelling of the quaternization starting material.
Cameron
Kenneth S
KS
Medicinal Chemistry Department, Organon Laboratories Ltd., Newhouse, ML1 5SH, Scotland, UK.
Morphy
J Richard
JR
Rankovic
Zoran
Z
York
Mark
M
D000586:Amination; D000588:Amines / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D005461:Fluorine; D009682:Magnetic Resonance Spectroscopy; D012117:Resins, Synthetic / Q000737:chemistry / Q000592:standards; D012997:Solvents / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D000588:Amines; D012117:Resins, Synthetic; D012997:Solvents; D005461:Fluorine