title: Synthesis of 5-amino- and 5-hydroxy-3,3-difluoropiperidines.
abstract: Synthetic routes toward new 5-amino- and 5-hydroxy-3,3-difluoropiperidines, which are of high interest as building blocks in medicinal chemistry, are described. The key step involves the N-halosuccinimide-induced cyclization of 2,2-difluoro-4-pentenylamines toward 5-halo-3,3-difluoropiperidines, which were used to synthesize 5-amino-3,3-difluoropiperidine. In a second strategy, iodolactonization of 2,2-difluoro-4-pentenoic acid gave the corresponding γ-lactone, which was transformed into 5-hydroxy-3,3-difluoropiperidine.
authors.affiliation: Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Surmont
authors.forename: Guido
authors.initials: G
authors.lastname: Verniest
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Thuring
authors.forename: Peter
authors.initials: P
authors.lastname: Ten Holte
authors.forename: Frederik
authors.initials: F
authors.lastname: Deroose
authors.forename: Norbert
authors.initials: N
authors.lastname: De Kimpe
mesh_terms: D003500:Cyclization; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D010421:Pentanoic Acids / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: C096093:2,2-difluoro-4-pentenoic acid; D006845:Hydrocarbons, Fluorinated; D007783:Lactones; D010421:Pentanoic Acids; D010880:Piperidines