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

Temperature

0 °C

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).

1. temperaturebefore cooling it again to −78° C
2. additionfollowed by a dropwise addition of a solution
3. additioncontaining
4. stirringThe solution was stirred at −78° C. for 2 hours
5. customThe reaction mixture was partitioned between a 1M solution of HCl and ether
6. extractionThe organic extract
7. washwas washed with a saturated solution of sodium bicarbonate and brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was purified on silica gel by flash column chromatography

ORD record

ord-6f07a11597824eb693df780c3143348c

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741931B2