Iodine → 4-Iodo-2-methoxy-5-((tetrahydro-2H-pyran-2-yl)oxy)pyridine

Temperature

-78 °C

At −78° C., 13.6 ml (90.1 mmol, 1.2 eq.) of 1,2-bis(dimethylamino)ethane and 54.0 ml (86.4 mmol, 1.15 eq.) of n-butyllithium were added to a solution of 16.2 g (75.1 mmol) of 2-methoxy-5-(tetrahydro-2H-pyran-2-yloxy)pyridine in 250 ml of THF, and the mixture was stirred at −78° C. for 1 h. 24.8 g (97.6 mmol, 1.3 eq.) of iodine were then added, and the reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to RT overnight. The reaction mixture was quenched with water and extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium thiosulphate solution, dried (sodium sulphate), filtered and concentrated under reduced pressure. Yield: 25.1 g (purity 82%, 82% of theory)

1. stirringthe reaction mixture was stirred at −78° C. for 1 h
2. temperatureto warm to RT overnight
3. customThe reaction mixture was quenched with water
4. extractionextracted three times with ethyl acetate
5. washThe combined organic phases were washed with saturated aqueous sodium thiosulphate solution
6. dry with materialdried (sodium sulphate)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-4dcf36fd43c1452aa4b6392c8b82171c

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434690B2