Dimethylformamide → 4-Bromopyridine-3-carbaldehyde

Temperature

-78 °C

A suspension of 4-bromopyridine hydrochloride (5.0 g, 25.7 mmol) in THF (100 mL) was purged with N2 and cooled to −78° C. A solution of lithium diisopropylamide (2.0 M solution in heptane/THF/ethylbenzene, 27.0 mL, 54.0 mmol) was added over 3 minutes. After 30 minutes, DMF (8.56 mL, 110.6 mmol) was added. The reaction mixture was stirred at −78° C. for 15 minutes before rapidly warming to room temperature in a water bath. The reaction was allowed to stir at ambient temperature for 18 hours. The reaction was quenched with saturated NH4Cl (100 mL) and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over Na2SO4, evaporated, and chromatographed (Analogix 150 g silica gel column eluting with a gradient of 100% heptane 50% EtOAc/heptane over 1 hour) to give 1.50 g (31%) of the title compound as a light yellow solid. MS m/z 186 (M+H)+.

1. customwas purged with N2
2. temperaturebefore rapidly warming to room temperature in a water bath
3. stirringto stir at ambient temperature for 18 hours
4. customThe reaction was quenched with saturated NH4Cl (100 mL)
5. extractionextracted with EtOAc
6. washThe combined organic extracts were washed with water and brine
7. dry with materialdried over Na2SO4
8. customevaporated
9. customchromatographed (Analogix 150 g silica gel column
10. washeluting with a gradient of 100% heptane 50% EtOAc/heptane over 1 hour)

ORD record

ord-86caee2ece1e45d5b95c03e1eda39be4

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260450B2