Iodine → 4-Iodo-2-methoxynicotinaldehyde

Temperature

-78 °C

A −78° C. solution of 2-methoxypyridine (40 g, 0.37 mol) in THF (1 L) was treated with t-BuLi (163 mL, 0.41 mol), stirred at −78° C. for 0.5 h, treated with N-(2-dimethylaminoethyl)-N-methylformamidine (52.9 g, 0.41 mol) over 10 min, stirred at −78° C. for another 0.5 h, then warmed to −20° C. for 45 minutes. The mixture was cooled to −40° C., treated with n-BuLi (289 mL, 0.46 mol), stirred at −40° C. for 1.5 h, then cooled to −78° C. The cold mixture was added via syringe to a solution of I2 (187.8 g, 0.74 mol) in THF at −78° C., stirred at −78° C. for 0.5 h, then warmed to 0° C. The mixture was quenched with satd. NaS2O3, the organic layer washed with brine, dried over Na2SO4, concentrated under reduce pressure, and purified by chromatography. The resulting solid was washed with pet ether to afford 4-iodo-2-methoxynicotinaldehyde (22 g, 23%). 1H NMR (400 MHz, CDCl3): δ 10.20 (s, 1H), 7.84 (d, J=5.6 Hz, 1H), 7.53 (d, J=5.2 Hz, 1H), 3.99 (s, 3H).

1. stirringstirred at −78° C. for another 0.5 h
2. temperaturewarmed to −20° C. for 45 minutes
3. temperatureThe mixture was cooled to −40° C.
4. stirringstirred at −40° C. for 1.5 h
5. temperaturecooled to −78° C
6. stirringstirred at −78° C. for 0.5 h
7. temperaturewarmed to 0° C
8. customThe mixture was quenched with satd
9. washNaS2O3, the organic layer washed with brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated
12. custompurified by chromatography
13. washThe resulting solid was washed with pet ether

ORD record

ord-6d194116cb81498995961657c28ff4b7

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012635B2