2-(2-Bromoethoxy)tetrahydro-2H-pyran → tert-Butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate
Reaktionsgleichung
[Br:1][C:2]1[N:3]=[C:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[NH:5][CH:6]=1.Br[CH2:21][CH2:22][O:23]C1CCCCO1>>[Br:1][C:2]1[N:3]=[C:4]([CH:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH2:12]2)[N:5]([CH2:21][CH2:22][OH:23])[CH:6]=1Komponenten
3
Versuchsvorschrift
tert-butyl 4-formylpiperidine-1-carboxylate 4a was reacted with aqueous glyoxal in the presence of aqueous ammonium hydroxide in methanol to give tert-butyl 4-(1H-imidazol-2-yl)piperidine-1-carboxylate 4b, which was bromined to afford tert-butyl 4-(4-bromo-1H-imidazol-2-yl)piperidine-1-carboxylate 4c. 4c was alkylated with 2-(2-bromoethoxy)tetrahydro-2H-pyran, followed by removal of THP group under acidic condition to yield tert-butyl 4-(4-bromo-1-(2-hydroxyethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate 4d. Suzuki coupling was performed with bromide intermediate 4d to afford 4e. 4e was reacted with methanesulfonyl chloride or 4-methylbenzenesulfonyl chloride, followed by quenching with amine afforded 4f, which was treated with hydrogen chloride in methanol or trifloruoacetic acid in DCM to provide the amine intermediates 4g.