1,3,5-Trifluoro-2-nitrobenzene → HCID 57625029, compound

HRID 1852388Notes

Reaction equation

HRID 1852388 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[N+:10]([O-:12])=[O:11].[F:13][C:14]1[CH:20]=[C:19]([I:21])[CH:18]=[CH:17][C:15]=1[NH2:16].C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>C1COCC1>[F:9][C:4]1[C:3]([N+:10]([O-:12])=[O:11])=[C:2]([CH:7]=[C:6]([F:8])[CH:5]=1)[NH:16][C:15]1[CH:17]=[CH:18][C:19]([I:21])=[CH:20][C:14]=1[F:13]

Participants

5

Reactant 3

HCID 675671,3,5-Trifluoro-2-nitrobenzeneHCID 1856942-Fluoro-4-iodoanilineHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 57625029HCID 57625029, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

25 g 1,3,5-trifluoro-2-nitrobenzene (141.2 mmol, 1 eq.) and 33.5 g 2-fluoro-4-iodoaniline (141.2 mmol. 1 eq.) were dissolved in 250 mL dry THF and cooled with ice-salt to −10 to 0° C. upon which 424 mL lithium hexamethyldisilazide (LiHMDS) solution (1M in THF; 424 mmol, 3. eq.) were added slowly over a 1 h periode. Upon completion of addition of base, the reaction mixtures was allowed to warm to rt and stirring was continued for 5 days. The reaction mixture was quenched with 0.5 N hydrochloric acid and diluted with ethyl acetate. Saturated ammonium chloride solution was added to facilitate phase separation. The separated aqueous phase was reextracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give dark solid residue. The residue was purified by flash column chromatography on silica gel with hexane and hexane/ethyl acetate 8:2 as eluent to yield 45.8 gram (82% yield) of the analytically pure target compound as a slightly brownish solid.

Workup

  1. additionwere added slowly over a 1 h periode
  2. additionUpon completion of addition of base
  3. customthe reaction mixtures
  4. customThe reaction mixture was quenched with 0.5 N hydrochloric acid
  5. additiondiluted with ethyl acetate
  6. additionSaturated ammonium chloride solution was added
  7. customphase separation
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give dark solid residue
  13. customThe residue was purified by flash column chromatography on silica gel with hexane and hexane/ethyl acetate 8:2 as eluent
  14. customto yield 45.8 gram (82% yield) of the analytically pure target compound as a slightly brownish solid

Sources & evidence

ORD record
ord-94fa81b8d2424d5eb19829b5393b1432
Source dataset
uspto-grants-2015_02
Patent number
US08962606B2

Reaction notes

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