Dichloromethane → 3-Nitro-2'-trifluoromethyl-biphenyl-4-ylamine

HRID 1518121Notes

Reaction equation

HRID 1518121 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.C(Cl)Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N+:9]([C:4]1[CH:3]=[C:2]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[C:13]([F:24])([F:23])[F:12])[CH:8]=[CH:7][C:5]=1[NH2:6])([O-:11])=[O:10]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 701324-Bromo-2-nitroanilineHCID 27343872-(Trifluoromethyl)benzeneboronic acid

Product 1

HCID 509940363-Nitro-2'-trifluoromethyl-biphenyl-4-ylamineYield 97.1%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

4-Bromo-2-nitroaniline (10.1 g, 46.7 mmol), 2-trifluoromethylphenylboronic acid (1.3 eq., 11.5 g, 60.7 mmol), and (dppf)PdCl2.DCM (0.05 eq., 1.91 g, 2.34 mmol) were placed in a 500 mL round-bottom flask equipped with a magnetic stir bar. The vial was evacuated and backflushed with Ar, and DME (180 mL) and 2M aq Na2 CO3 (60 mL) were added via syringe. The flask was capped tightly, and the reaction was stirred at 90° C. for 16 h. The reaction was cooled to RT, diluted with EtOAc, and washed sequentially with water and brine. The organic extract was dried over anhydrous MgSO4, filtered, and the solvent was removed under reduced pressure. The crude product was dry-loaded onto 25 g of SiO2 and purified by column chromatography using an 80-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 20 min, yielding 12.8 g (97%) of the desired compound. 1H-NMR (400 MHz, CDCl3) δ: 8.11 (d, J=2.0 Hz, 1H), 7.75 (d, J=7.8 Hz, 1H), 7.54-7.62 (m, J=7.6 Hz, 1H), 7.44-7.53 (m, J=7.8 Hz, 1H), 7.36 (dd, J=8.6, 1.3 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 6.84 (d, J=8.6 Hz, 1H).

Workup

  1. customequipped with a magnetic stir bar
  2. customThe vial was evacuated
  3. additionCO3 (60 mL) were added via syringe
  4. customThe flask was capped tightly
  5. temperatureThe reaction was cooled to RT
  6. additiondiluted with EtOAc
  7. washwashed sequentially with water and brine
  8. extractionThe organic extract
  9. dry with materialwas dried over anhydrous MgSO4
  10. filtrationfiltered
  11. customthe solvent was removed under reduced pressure
  12. custompurified by column chromatography
  13. washeluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 20 min

Sources & evidence

ORD record
ord-7a45897dbd304d08aad2623603e57c03
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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