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

Temperature

-78 °C

To a flame-dried 100 mL round-bottomed flask, was added dry THF (15 mL). The solution was cooled to −78° C. and then N,N-diisopropylamine (0.46 mL, 3.28 mmol), 2.5M n-butyllithium in hexane (1.31 mL, 3.28 mmol), and a solution of the compound from Step B above (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 (0.276 mL, 4.49 mmol) was slowly added. After the reaction was stirred for another 2 h, the mixture was warmed and stirred for 30 min at room temperature. Then the mixture was quenched by the addition of saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic phases were washed sequentially with water and saturated brine, dried over sodium sulfate and concentrated. The residue was purified by flash chromatography (silica gel; 15% ethyl acetate/hexanes as eluant) to yield the title compound. 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 by the addition of saturated aqueous ammonium chloride solution
5. extractionextracted with ethyl acetate
6. washThe combined organic phases were washed sequentially with water and saturated brine
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated
9. customThe residue was purified by flash chromatography (silica gel; 15% ethyl acetate/hexanes as eluant)

ORD record

ord-f846e4adda544278b022de3f36b663cf

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07388019B2