2,2,6,6-Tetramethylpiperidine → 6-Chloro-2-iodo-3-(trifluoromethyl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,2,6,6-tetramethylpiperidine (4.277 g, 5.110 mL, 30.28 mmol) in THF (18.00 mL) cooled to −78° C. was added nBuLi in hexanes (11.72 mL of 2.5 M, 29.30 mmol). The solution was allowed to warm up to 0° C. and was stirred for 15 minutes at that temperature before cooling it again to −78° C. Iodine (12.40 mg, 2.515 μL, 0.04884 mmol) was added followed by a dropwise addition of a solution containing a mixture of 2-chloro-3-iodo-5-(trifluoromethyl)pyridine (2 g, 6.505 mmol) and 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (4.000 g, 13.01 mmol) in THF (18.00 mL). The solution was stirred at −78° C. for 2 hours. The reaction mixture was partitioned between a 1M solution of HCl and ether. The organic extract was washed with a saturated solution of sodium bicarbonate and brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound as a pale yellow oil (1.92 g, 32% yield).

Provenance & Evidence