Tetrahydrofuran → 6-Bromopyridine-2-carbaldehyde

Temperature

-78 °C

To a solution of 23.7 g (100 mmol) of 2,6-dibromopyridine in 150 mL of anhydrous, degassed THF cooled to −78° C. was added dropwise under N2 a solution of 11.0 mL (110 mmol) of 10.0 M n-BuLi in 150 mL anhydrous, degassed Et2O. After 2 hours at −78° C., 24.2 mL (300 mmol) of anhydrous degassed DMF was added dropwise with rapid stirring. This solution was stirred at −78° C. for 2 hours, and was then allowed to warm to room temperature (RT) overnight. The solution was cooled to −78° C. and 100 mL of 1.0 M aq. HCl was added slowly. The organic phase was separated and the aqueous phase was washed with 3×50 mL Et2O. The organic washes were combined and washed with 3×50 mL H2O and 3×50 mL brine, then dried over Na2SO4. The volatiles were removed in vacuo to provide an orange oil. The oil was triturated with hexanes to give 2-bromo-6-formylpyridine as a pale orange solid that was washed with cold pentanes and dried under vacuum overnight.

1. customdegassed Et2O
2. custom24.2 mL (300 mmol) of anhydrous degassed DMF
3. additionwas added dropwise with rapid stirring
4. temperatureto warm to room temperature (RT) overnight
5. temperatureThe solution was cooled to −78° C.
6. addition100 mL of 1.0 M aq. HCl was added slowly
7. customThe organic phase was separated
8. washthe aqueous phase was washed with 3×50 mL Et2O
9. washwashed with 3×50 mL H2O and 3×50 mL brine
10. dry with materialdried over Na2SO4
11. customThe volatiles were removed in vacuo
12. customto provide an orange oil
13. customThe oil was triturated with hexanes

ORD record

ord-120986a62ff94adc98e78a1295f06593

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07425661B2