Triethylamine → 1,1-Dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of N-Boc-4-piperidinemethanol (4.8 g, 22.3 mmol), Et3N (3.4 mL, 24.5 mmol) in CH2Cl2 (100 mL) at 0° C. was treated dropwise with methanesulfonyl chloride (1.8 mL, 23.4 mmol). The reaction mixture was stirred at 0° C. for 1 h, and then was washed with water twice. The CH2Cl2 layer was dried over MgSO4, filtered, and the filtrate was concentrated. The residue was mixed with 6-bromo-3-pyridinol (3.88 g, 22.3 mmol) and K2CO3 (6.2 g, 44.6 mmol) in DMF (50 mL). The resulting mixture was heated at 90° C. overnight, cooled to ambient temperature, sat overnight, then was quenched with water and stirred at room temperature for 4 h. The resulting precipitate was collected, washed with water, and air-dried. The crude product was purified by chromatography on a silica gel column using 0 to 10% MeOH/CH2Cl2 to give 3.6 g (43%) of 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate as a white solid along with some impure material. The impure material was repurified by chromatography on a silica gel column using 0 to 2.5% MeOH/CH2Cl2 to give an additional 2.8 g (77% overall yield) of 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate as an off-white solid.

Provenance & Evidence