Synthesis of 2,2,6,6-tetrafluoro-4-phenylmethylmorpholin-3-ones: A simple approach from fluorinated triethylene glycol

2,2,6,6-Tetrafluoro-4-phenylmethylmorpholin-3-ones are obtained from a new single step, preparative route by reacting triethylene glycol di(trifluoromethanesulfonate), which contains poly –CF2O– groups, with benzylamine. Reaction of trifluoromethylsulfonate and trifluoromethoxy derivatives with benzylamine gave either the nucleophilically-substituted product or the product resulting from the basic hydrolysis of the difluoromethoxy group. Replacement of a fluoroether chain by a fluoroalkane gave rise to fluorinated phenylmethylpiperidine and phenylmethylazepine via the combination of trifluoromethanesulfonic fluoroalkyldiyl esters and benzylamine.

Graphical abstractA new synthetic routine was developed for the synthesis of 2,2,6,6-tetrafluoro-4-phenylmethyl-morpholin-3-one by a single step combination of fluorinated triethylene glycol di(trifluoromethanesulfonate) and benzylamine. With a fluoroalkane di(trifluoromethanesulfonate), fluorinated phenylmethylpiperidine and phenylmethylazepine were synthesized by reaction of trifluoromethanesulfonic fluoroalkyldily esters and benzylamine.Figure optionsDownload full-size imageDownload as PowerPoint slide