Diisopropylamine → 3-Bromopyridine-4-carboxaldehyde

Temperature

-60 °C

A solution of di-isopropylamine (3.44 g, 34.1 mmol) was cooled to -78° C. and treated with n-butyl lithium 1.6M, 34.1 mmol). A solution of 3-bromopyridine (4.71 g, 30 mmol) in THF (5 ml) was added dropwise trying to keep the temperature below -70° C. The reaction was very exothermic, a solid precipitated and THF (2 ml) was added to improve stirring. The temperature rose to -45° C., after cooling to -60° C. and added remaining pyridine. DMF (2.49 g) in THF (15 ml) was added and the reaction stirred at -65° C. for 30 minutes. Water was added to quench the reaction and the reaction allowed to warm to ambient temperature. The reaction was partitioned between ethyl acetate/water and the aqueous layer extracted with ethyl acetate. The organic layers were combined, dried (MgSO4) and evaporated and the residue was subjected to chromatography (eluting with diethyl ether/hexane) to give 3-bromo-4-pyridinecarbaldehyde (1.4 g, 76%).

1. customthe temperature below -70° C
2. customa solid precipitated
3. additionTHF (2 ml) was added
4. customrose to -45° C.
5. additionadded
6. additionDMF (2.49 g) in THF (15 ml) was added
7. stirringthe reaction stirred at -65° C. for 30 minutes
8. additionWater was added
9. customto quench
10. customthe reaction
11. temperatureto warm to ambient temperature
12. customThe reaction was partitioned between ethyl acetate/water
13. extractionthe aqueous layer extracted with ethyl acetate
14. dry with materialdried (MgSO4)
15. customevaporated
16. washthe residue was subjected to chromatography (eluting with diethyl ether/hexane)

ORD record

ord-ab513a2ce80d46edaa1872a30538589c

Source dataset

uspto-grants-1998_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05834468