1,2,3-Trifluoro-4-nitrobenzene → HCID 68981237, compound

HRID 1822147Notes

Reaction equation

HRID 1822147 reaction equation
[C:1]([NH:5][C:6]([C:8]1[CH:9]=[C:10]([OH:21])[CH:11]=[C:12]([C:14](=[O:20])[NH:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].F[C:29]1[C:34]([F:35])=[C:33]([F:36])[CH:32]=[CH:31][C:30]=1[N+:37]([O-:39])=[O:38]>C1COCC1>[C:1]([NH:5][C:6](=[O:7])[C:8]1[CH:9]=[C:10]([O:21][C:29]2[C:30]([N+:37]([O-:39])=[O:38])=[CH:31][CH:32]=[C:33]([F:36])[C:34]=2[F:35])[CH:11]=[C:12]([C:14]([NH:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:20])[CH:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 698711,2,3-Trifluoro-4-nitrobenzeneHCID 23665647Potassium tert-butoxideHCID 68983550HCID 68983550, compound

Product 1

HCID 68981237HCID 68981237, compoundYield 88.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 22 L round-bottom flask was charged with 3,5-bis-tert-butylcarbamoyl-phenol (20, 360 g, 1.23 mol) and THF (12.5 L). The resulting slurry was cooled to 0° C. and potassium tert-butoxide (1.35 L, 1.0 M in THF, 1.35 mol) was added dropwise over approximately 30 min. After the addition was complete, the reaction mixture was cooled to between −30 and −35° C. and 2,3,4-trifluoronitrobenzene (239, 1.35 mol) was added dropwise over approximately 5 min. The reaction mixture was stirred at approximately −30° C. for 1 h whereupon the cooling bath was removed. The reaction mixture was then stirred for 20 h with warming to ambient temperature. A mixture of water (2.0 L) and brine (1.0 L) was added, and the reaction mixture was stirred vigorously in a 20 L extractor ball. Following removal of the aqueous phase, the organic layer was washed with additional brine (1.5 L), and the resulting THF solution was transferred to a 22 L round bottom flask for distillation. The extractor ball was rinsed with THF (500 mL). After approximately 10 L of THF had been removed by distillation, addition of isopropyl alcohol (11 L) was initiated and the distillation was continued until approximately 23 L of distillate had been collected. When the residual volume was 5 L and the pot temperature was 82° C., water (2.0 L) was added dropwise. Heating was then discontinued, and the reaction mixture was stirred overnight with cooling to room temperature. The resulting solid was filtered through a 3 L course-frit sintered glass filter funnel. The filter cake was washed with IPA/H2O (1:1, 2×600 mL) and dried in a vacuum oven (70° C., 25 Torr) to afford N,N′-di-tert-butyl-5-(2,3-difluoro-6-nitro-phenoxy)-isophthalamide (21; 488 g, 88% theory).

Workup

  1. additionAfter the addition
  2. temperaturethe reaction mixture was cooled to between −30 and −35° C.
  3. customwas removed
  4. stirringThe reaction mixture was then stirred for 20 h
  5. temperaturewith warming to ambient temperature
  6. additionA mixture of water (2.0 L) and brine (1.0 L)
  7. additionwas added
  8. stirringthe reaction mixture was stirred vigorously in a 20 L extractor ball
  9. customremoval of the aqueous phase
  10. washthe organic layer was washed with additional brine (1.5 L)
  11. distillationthe resulting THF solution was transferred to a 22 L round bottom flask for distillation
  12. washThe extractor ball was rinsed with THF (500 mL)
  13. customAfter approximately 10 L of THF had been removed by distillation, addition of isopropyl alcohol (11 L)
  14. distillationthe distillation
  15. customhad been collected
  16. customwas 82° C.
  17. additionwater (2.0 L) was added dropwise
  18. temperatureHeating
  19. stirringthe reaction mixture was stirred overnight
  20. temperaturewith cooling to room temperature
  21. filtrationThe resulting solid was filtered through a 3 L course-frit sintered glass
  22. filtrationfilter funnel
  23. washThe filter cake was washed with IPA/H2O (1:1, 2×600 mL)
  24. customdried in a vacuum oven (70° C., 25 Torr)

Sources & evidence

ORD record
ord-6a786bdc29c142c1ba0468cbc785ca3c
Source dataset
uspto-grants-2009_10
Patent number
US07608731B2

Reaction notes

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