Methyl formate → 3,5-Dibromo-2-methoxy-6-(trifluoromethyl)pyridine-4-carbaldehyde

To a flame-dried 100 mL round-bottomed flask, was added dry THF (15 mL). The solution was cooled to −78° C. before diisopropylamine (460 μL, 3.28 mmol), 2.5 M n-butyllithium in hexane (1.31 mL, 3.28 mmol), and a solution of 3,5-dibromo-2-methoxy-6-(trifluoromethyl)pyridine (1.00 g, 2.99 mmol) in dry THF (10 mL), were added sequentially. The reaction mixture was stirred at −78° C. for 10 min before methyl formate (276 μL, 4.49 mmol) was slowly added. After the reaction was stirred for another 2 hr, the mixture was warmed and stirred for 30 min at room temperature. Then the mixture was quenched with saturated ammonium chloride solution, extracted with EtOAc, washed by water and brine, dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography (silica gel, 15% EtOAc/hexanes) to yield 3,5-dibromo-2-methoxy-6-(trifluoromethyl)isonicotinaldehyde (985 mg, 90.5%). 1H-NMR (400 MHz, CDCl3) δ 10.10 (s, 1H), 4.11 (s, 3H).

1. additionwas slowly added
2. temperaturethe mixture was warmed
3. stirringstirred for 30 min at room temperature
4. customThen the mixture was quenched with saturated ammonium chloride solution
5. extractionextracted with EtOAc
6. washwashed by water and brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customThe residue was purified by flash column chromatography (silica gel, 15% EtOAc/hexanes)

ORD record

ord-8e6cc88cca344e46ac0599a51a5068de

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07393844B2