Hydrochloric Acid → 4-(2-Chloro-5-fluoro-phenoxy)-piperidine hydrochloride
Reaktionsgleichung
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[Cl:22])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>C(OCC)(=O)C>[ClH:22].[Cl:22][C:16]1[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=1[O:14][CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1Komponenten
4
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Versuchsvorschrift
To a stirred solution of 2-chloro-5-fluorophenol (6 g, 0.0413 mole) in DMF (20 mL) was added cesium carbonate (26.89 g, 0.00827 mole) followed by 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (11.54 g, 0.04137 mole). The reaction mixture was heated at 80° C. for overnight. The mixture was then diluted with water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 230-400 mesh (2% ethyl acetate in hexane) to afford 8.9 g (65%) of 4-(2-chloro-5-fluoro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. LCMS: 330.12 (M+1)+, 100%. A solution of 4-(2-chloro-5-fluoro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (8.9 g, 0.027 mole) in ethyl acetate.HCl (10 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was then concentrated under reduced pressure and the resulting residue was washed with ether to afford 6.54 g (92%) of. LCMS: 230.07 (M+1)+, 100%, 1H NMR (DMSO-d6): δ 9.6-9.1 (bs, 2H), 7.55-7.45 (t, 1H), 7.35-7.2 (d, 1H), 6.9-6.8 (t, 1H), 4.9-4.7 (s, 1H), 3.26-3.0 (s, 4H), 2.2-2.06 (s, 2H), 2.0-1.8 (s, 2H).