Dimethylformamide → 4-Bromopyridine-3-carbaldehyde

Temperature

-78 °C

A suspension of 4-bromopyridine (13.7 g, 86.8 mmol) in 300 mL THF was purged with N2 and cooled to −78° C. under an atmosphere of dry N2. A solution of lithium diisopropylamide (2.0 M solution in heptane/THF/ethylbenzene, 43.4 mL, 86.8 mmol) was added over about 3 minutes. After 30 minutes, DMF (dimethylformamide) was added. The reaction mixture was maintained at −78° C. for 3 hours before allowing it to warm to ambient temperature overnight. The reaction mixture was quenched with saturated NH4Cl and concentrated under reduced pressure to remove most of the THF. The aqueous mixture was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over Na2SO4, evaporated, and chromatographed (150 g Analogix silica gel column eluting with a gradient of 100% heptane to 30% EtOAc/heptane over 45 minutes). Fractions containing the product were combined and evaporated to give 2.20 g (13.6%) of the title compound. MS m/z 186 (M+H)+.

1. customwas purged with N2
2. temperatureThe reaction mixture was maintained at −78° C. for 3 hours
3. temperatureto warm to ambient temperature overnight
4. customThe reaction mixture was quenched with saturated NH4Cl
5. concentrationconcentrated under reduced pressure
6. customto remove most of the THF
7. extractionThe aqueous mixture was extracted with EtOAc
8. washThe combined organic extracts were washed with water and brine
9. dry with materialdried over Na2SO4
10. customevaporated
11. customchromatographed (150 g Analogix silica gel column
12. washeluting with a gradient of 100% heptane to 30% EtOAc/heptane over 45 minutes)
13. additionFractions containing the product
14. customevaporated

ORD record

ord-4877f9ae95654b64a96397337d2e8e02

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090625B2