Sulfuric Acid → Tert-butyl 2-(2,3-difluoro-6-nitrophenyl)-3-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

To toluene (810 1) was charged sodium tert-pentoxide (91 kg, 2.3 eq). The mixture was heated to 40° C. and tert-butyl acetoacetate (124.3 kg, 2.2 eq) added. The mixture was heated to 70° C. and trifluoronitrobenzene (63.1 kg, 1.0 eq) added. The temperature was maintained at 70° C. for 3 hours. The mixture was cooled to 25° C. and 20% w/w sulphuric acid added to adjust the pH to 5. The lower aqueous layer was discarded and the organic layer washed twice with water (2×227 kg of water), with 2.3% w/w sodium bicarbonate (192 kg) and then water (192 kg). The organic layer was distilled under vacuum (50 mbar), removing 574 kg of distillate leaving a solution of tert-butyl 2-(2,3-difluoro-6-nitrophenyl)-3-oxobutanoate in toluene.

Provenance & Evidence