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

Temperature

0 °C

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.

1. washwas washed with water twice
2. dry with materialThe CH2Cl2 layer was dried over MgSO4
3. filtrationfiltered
4. concentrationthe filtrate was concentrated
5. temperatureThe resulting mixture was heated at 90° C. overnight
6. temperaturecooled to ambient temperature
7. waitsat overnight
8. customwas quenched with water
9. stirringstirred at room temperature for 4 h
10. customThe resulting precipitate was collected
11. washwashed with water
12. customair-dried
13. customThe crude product was purified by chromatography on a silica gel column

ORD record

ord-9a0051297d6c41ddb4f0ca1f67a1c0f7

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101634B2