Ethyl formate → 3-Bromo-5-chloropyridine-4-carboxaldehyde

Temperature

-78 °C

A solution of LDA (7.94 mL, 1.8 M in THF/heptane/ethylbenzene, 14.3 mmol) in anhydrous THF (30 mL) at −78° C. under Ar was treated dropwise with a solution of 3-bromo-5-chloro-pyridine (2.5 g, 13.0 mmol) in anhydrous THF (30 mL) The solution was stirred at −78° C. for 30 min, then a solution of ethyl formate (10.46 mL, 130 mmol) in anhydrous THF (30 mL) was added dropwise. The resulting solution was stirred at −78° C. for 1.5 h and then treated with saturated NaHCO3 with vigorous stirring. The quenched mixture was extracted with EA (2×25 mL) and the combined organic extracts were washed with saturated NaHCO3 (15 mL) and dried over Na2SO4. The residue was purified by flash chromatography on silica gel with EA/hexane to provide 3-bromo-5-chloro-pyridine-4-carbaldehyde as a yellow solid. Reduction of the aldehyde according to the synthesis of (3,5-dichloro-pyridin-4-yl)-methanol yielded the title compound. MS (m/z): 224.0 [M+H+].

1. stirringThe resulting solution was stirred at −78° C. for 1.5 h
2. extractionThe quenched mixture was extracted with EA (2×25 mL)
3. washthe combined organic extracts were washed with saturated NaHCO3 (15 mL)
4. dry with materialdried over Na2SO4
5. customThe residue was purified by flash chromatography on silica gel with EA/hexane

ORD record

ord-cd9b7f9448ee4b01a52cbde25719023c

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410134B2