Dimethylformamide → 2-Bromo-5-chloropyridine-4-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

To a stirred sol. of diisopropylamine (20.9 mL, 148 mmol) in dry THF (350 mL) at −5° C. was added dropwise BuLi (1.6M in hexane, 89.5 mL, 143 mmol), and the resulting sol. was stirred for 30 min at −5° C. The sol. was allowed to cool to −70° C., and a sol. of 2-bromo-5-chloropyridine (25.0 g, 130 mmol) in THF (100 mL) was added dropwise at −70° C. over 15 min such as the internal temperature did not exceed −65° C. The mixture was stirred at −70° C. for 30 min. DMF (10.5 mL, 136 mmol) was added dropwise over 20 min at such a rate that the internal temperature did not exceed −70° C. The orange mixture was stirred at −70° C. for 40 min. The mixture was allowed to warm up to rt, and was poured onto a mixture of water (200 mL) and aq. 1M NaOH (50 mL). The mixture was extracted with EtOAc (2×), and the combined org. extracts were washed back with aq. 1M NaOH (2×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:9→1:8→1:6→1:4→1:2→1:1) yielded the title compound (21.6 g, 72%). LC-MS: tR=0.74 min; ES+: 295.01.

Provenance & Evidence