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

Temperature

-5 °C

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.

1. temperatureto cool to −70° C.
2. customdid not exceed −65° C
3. stirringThe mixture was stirred at −70° C. for 30 min
4. customdid not exceed −70° C
5. stirringThe orange mixture was stirred at −70° C. for 40 min
6. temperatureto warm up to rt
7. extractionThe mixture was extracted with EtOAc (2×)
8. washextracts were washed back with aq. 1M NaOH (2×)
9. dry with materialextracts were dried over MgSO4
10. filtrationfiltered
11. customthe solvents were removed under reduced pressure
12. customPurification of the crude by FC (EtOAc/heptane 1:9→1:8→1:6→1:4→1:2→1:1)

ORD record

ord-725a37c221ef40ae88af432d733d6001

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968720B2