Synthesis of 5-amino- and 5-hydroxy-3,3-difluoropiperidines.
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.
Surmont
Riccardo
R
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Verniest
Guido
G
Thuring
Jan Willem
JW
Ten Holte
Peter
P
Deroose
Frederik
F
De Kimpe
Norbert
N
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
C096093:2,2-difluoro-4-pentenoic acid; D006845:Hydrocarbons, Fluorinated; D007783:Lactones; D010421:Pentanoic Acids; D010880:Piperidines