Methyl formate → 3,5-Difluoropyridine-4-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

Under argon and at −70° C., 44 ml of 2.5 M n-butyllithium solution in n-hexane (110 mmol, 1.1 equivalent) were slowly added dropwise to 15.4 ml of diisopropylamine (110 mmol, 1.1 equivalent) in 23 ml of THF. The solution formed was warmed to 0° C. and stirred at this temperature for 30 min. The reaction mixture was then brought to −70° C. and diluted with 23 ml of THF, and 11.5 g of 3,5-difluoropyridine (100 mmol, 1 equivalent) dissolved in 72 ml of THF, were added dropwise. The mixture was stirred at −70° C. for 30 min. 12.4 ml of methyl formate (200 mmol, 2 equivalent), dissolved in 23 ml of THF, were then slowly added dropwise. After 1.5 h at −70° C., the reaction solution was quickly poured into 230 ml of saturated aqueous sodium bicarbonate solution and extracted with a total of 460 ml of ethyl acetate. The combined organic phases were washed twice with in each case 115 ml of saturated aqueous sodium bicarbonate solution and twice with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated using a rotary evaporator. This gave 11.6 g (81% of theory) of the title compound which were directly reacted further.

Provenance & Evidence