Sodium hydride → 3-Chloro-2-[4-(bis-[1,1-dimethylethoxycarbonyl]methyl)-3-nitrophenyl]-5-trifluoromethylpyridine

Participants

Reaction Steps

0.9 g of an 80% strength by weight suspension of sodium hydride in mineral oil was added to 10 ml of anhydrous dimethylformamide. A solution of 5.1 g of di-tert-butyl malonate in 20 ml of dimethylformamide was added dropwise to this mixture, after which it was stirred for 30 minutes. A solution of 7.5 g of 3-chloro-2-(4-fluoro-3-nitrophenyl)-5-trifluoromethylpyridine in 20 ml of dimethylformamide was then added dropwise. The reaction mixture was stirred at 23° C. for 20 hours and at 80° C. for 5 hours. The cooled reaction mixture was then poured into 200 ml of ice water. The aqueous phase was extracted three times with 100 ml of tert-butyl methyl ether each time. The combined organic phases were washed with 100 ml of water, dried over sodium sulfate and concentrated. Yield: 10.8 g (79%) of a colorless oil.

Provenance & Evidence