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 (5.0 g, 23.22 mmol), Et3N (4.85 mL, 34.83 mmol) in CH2Cl2 (100 mL) at 0° C. was treated dropwise with methanesulfonyl chloride (2.16 mL, 27.86 mmol). The reaction mixture was stirred at 0° C. for 0.5 h, diluted with CH2Cl2 and washed with water and brine. The CH2Cl2 layer was dried over Na2SO4, filtered, and the filtrate was concentrated. The residue was mixed with 6-bromo-3-pyridinol (6.06 g, 34.83 mmol) and K2CO3 (6.41 g, 46.44 mmol) in DMF. The resulting mixture was heated at 65° C. overnight, cooled to ambient temperature and partitioned between water and EtOAc. The organic layer was separated and washed with 2N NaOH, water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product, which was purified by chromatography on a silica gel column to give 5.88 g (68%) of 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate. 1H NMR (400 MHz, CDCl3): δ 8.00 (1H, d, J=3.1 Hz), 7.32 (d, 1H, J=8.6 Hz), 7.05 (dd, 1H, Ja=8.7 Hz, Jb=3.2 Hz), 4.13 (bs, 2H), 3.79 (d, 2H, J=6.5 Hz), 2.80-2.65 (m, 2H), 2.00-1.85 (m, 1H), 1.80-1.70 (m, 2H), 1.43 (s, 9H), 1.30-1.15 (m, 2H).

Provenance & Evidence