Water → Tert-butyl 4-[2-(2-tert-butylphenoxy)ethyl]piperidine-1-carboxylate

Beteiligte Stoffe

Reaktionsschritte

To an ice-cold stirred solution of tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate (44.3 g, 193 mmol) in pyridine (30.0 mL) was added p-TsCl (5.63 g, 30.0 mmol). After stirring for 16 h at room temperature, the reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate (300.0 ml) and 1.0 N hydrochloric acid (200.0 mL) and separated. The organic layer was washed with water (2×100 mL), saturated sodium chloride (100 mL), dried (MgSO4), filtered and filtrate concentrated under reduced pressure. The residue was dissolved in DMF (100.0 mL), added to a stirred solution of 2-(tert-butyl)phenol (10.8 g, 72.0 mmol) and K3PO4 (45.8 g, 216 mmol) in DMF (60.0 mL) and the resulting reaction mixture was heated at 80° C. for 16 h. Then, the reaction mixture was cooled to room temperature, poured into water (150.0 mL) and extracted with ethyl acetate (2×100.0 mL). The combined organics were washed with water (2×150 ml), saturated sodium chloride (100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 95:5 to 90:10 hexane/ethyl acetate) to provide tert-butyl 4-[2-(2-tert-butylphenoxy)ethyl]piperidine-1-carboxylate (31.7 g, 44%) as a yellow oil.

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