2-Chlorophenol → Tert-butyl 4-(2-chlorophenoxy)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-chlorophenol (20 g, 0.155 mole) in DMF (200 mL), was added cesium carbonate (101 g, 0.311 mole), followed by 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (43.45 g, 0.155 mole). The reaction mixture was heated at 65° C. for 7 hours. The mixture was then filtered and concentrated under reduced. The resulting residue was diluted with ice cold water and the solid obtained was filtered and washed with water. The solid was dissolved in ether, washed with 2.5N aqueous NaOH solution, dried over sodium sulfate and concentrated under reduced pressure to afford 24.24 g (50%) of 4-(2-chloro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. LCMS: 312.13 (M+1)+, 98.35%. A solution of 4-(2-chloro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester (24.2 g, 0.0776 mole) in dioxane.HCl (30 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 hexane twice to afford 19.13 g (99.6%) of 4-(2-chloro-phenoxy)-piperidine hydrochloride. LCMS: 248.05 (M+1)+, 92.79%. 1H NMR (DMSO-d6): δ 9.3-8.9 (bs, 2H), 7.5-7.42 (d, 1H), 7.38-7.24 (m, 2H), 7.04-6.94 (t, 2H), 4.8-4.7 (m, 1H), 3.3-3.0 (bd, 4H), 2.2-2.05 (bs, 2H), 2.0-1.8 (bs, 2H).

Provenance & Evidence