A facile method for converting alcohol to thioether and its application in the synthesis of a novel GPR119 agonist

We studied a modified Mitsunobu reaction for the direct conversion of alcohol to thioether, resulting in a high yield and requiring fewer steps. A facile method for synthesizing a novel GPR119 agonist, (R)-1,1,1-trifluoropropan-2-yl-6-(4-(((pyridin-2-ylmethyl)sulfonyl)methyl)phenyl)spiro[chromane-2,4′-piperidine]-1′-carboxylate (1), was established starting from the key intermediate alcohol 3 to pyridylmethylthioether 14 by using PPh3(OCH2CF3)2 without protection of the piperidine moiety, resulting in an excellent yield. Finally, the efficient oxidation of the sulfide and carbamoylation of the piperidine moiety afforded the desired product 1.

Graphical abstractDownload full-size image