Hydrochloric Acid → 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde

Temperature

-78 °C

A flask was charged with 4-chloro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (25.2 g, 82.0 mmol) in THF (400 mL) and cooled to about −78° C. sec-BuLi (1.4 M in cyclohexane, 116 mL, 163 mmol) was added drop-wise over about 15 min. The mixture was stirred at −78° C. for about 1 h. To the mixture was added DMF (18.9 mL, 245 mmol) drop-wise and the temperature was maintained at about −78° C. for about 1 h. The mixture was quenched by the slow addition of a solution of HCl (4.0 M in 1,4-dioxane, 20.4 mL, 82.0 mmol) followed by the addition of saturated aqueous NaHCO3 (100 mL). The mixture was extracted with EtOAc (500 mL). The organic layer was allowed to sit at rt overnight. The precipitate formed was collected by filtration. The filtrate formed more precipitate which was collected by filtration again. The precipitated material from both filtrations was combined to give 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (12.9 g, 88%): LC/MS (Table 2, Method a) Rt=1.85 min; MS m/z 181 (M+H)+

1. additionwas added drop-wise over about 15 min
2. temperaturethe temperature was maintained at about −78° C. for about 1 h
3. extractionThe mixture was extracted with EtOAc (500 mL)
4. waitto sit at rt overnight
5. customThe precipitate formed
6. filtrationwas collected by filtration
7. customThe filtrate formed more precipitate which
8. filtrationwas collected by filtration again
9. filtrationThe precipitated material from both filtrations

ORD record

ord-7e8fab2b32744fee977cdae207b2f258

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785639B2