A [2 + 2] cycloaddition route to dimethylaminomethylene vinamidinium salts.
[reaction: see text] Trifluoropropanoic acid reacts with 1 equiv of POCl3 in DMF to generate the trifluoromethyl enamine (7). At this stage, two reaction manifolds are available. The expected reaction with additional POCl3 generates the 2-trifluoromethyl vinamidinium salt (3c). However, thermally driven loss of fluoride generates an iminium ion, which sets the stage for a [2 + 2] cycloaddition to ultimately generate the dimethylaminomethylene vinamidinium salt (1).
Department of Process Research and the Reaction Engineering Laboratory of Chemical Engineering R&D, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. ian_davies1@merck.com
Ian W
IW
Davies
David M
DM
Tellers
C Scott
CS
Shultz
Fred J
FJ
Fleitz
Dongwei
D
Cai
Yongkui
Y
Sun
D002626:Chemistry, Pharmaceutical; D004123:Dimethylamines / Q000138:chemical synthesis*; D005466:Fluorocarbons / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007097:Imines / Q000737:chemistry; D014747:Vinblastine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D014753:Vinyl Compounds / Q000737:chemistry
D004123:Dimethylamines; D005466:Fluorocarbons; D006571:Heterocyclic Compounds; D007097:Imines; D014753:Vinyl Compounds; C476089:dimethylaminomethylene vinamidinium salt; D014747:Vinblastine