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

HRID 407266Notes

Reaction equation

CCC([O-])(C)C.[Na+].[C:8]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])[CH2:9][C:10]([CH3:12])=[O:11].[F:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22](F)[C:21]=1[F:30].S(=O)(=O)(O)O>C1(C)C=CC=CC=1>[F:30][C:21]1[C:20]([F:19])=[CH:25][CH:24]=[C:23]([N+:26]([O-:28])=[O:27])[C:22]=1[CH:9]([C:10](=[O:11])[CH3:12])[C:8]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

Conditions

Temperature: 40 °C

Procedure

To toluene (810 l) 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.

Workup

temperatureThe mixture was heated to 70° C.
temperatureThe temperature was maintained at 70° C. for 3 hours
temperatureThe mixture was cooled to 25° C.
washthe organic layer washed twice with water (2×227 kg of water), with 2.3% w/w sodium bicarbonate (192 kg)
distillationThe organic layer was distilled under vacuum (50 mbar)
customremoving 574 kg

Sources & evidence

ORD record: ord-213f0d7dc75f4291b646011682d2f347
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754240B2

Reaction notes

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