Potassium Phosphate, Tribasic → HCID 66599487, compound

HRID 2410814Notes

Reaction equation

HRID 2410814 reaction equation
[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9](Br)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[C:11]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)=[N:10][C:9]([C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([C:23]([F:34])([F:33])[F:22])[CH:29]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86663047HCID 86663047, compound

Product 1

HCID 66599487HCID 66599487, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A flask containing a mixture of methyl 3-amino-6-bromo-2-(4-nitrophenyl)isonicotinate (1.70 g, 4.83 mmol), 3-(trifluoromethyl)phenylboronic acid (1.83 g, 9.66 mmol), powdered potassium phosphate tribasic (3.38 g, 15 9 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (0.460 g, 0.966 mmol), and Pd(OAc)2 (0.108 g, 0.483 mmol) was flushed with nitrogen. THF (20 mL) was added and the mixture was heated at reflux under nitrogen for 2 hr. The mixture was diluted with EtOAc and washed with water and brine. After drying with Na2SO4), the solvents removed and the residue was suspended in a mixture of 20% EtOAc in hexane. Filtration afforded methyl 3-amino-2-(4-nitrophenyl)-6-(3-(trifluoromethyl)phenyl)-isonicotinate (1.0 g, 2.2 mmol, 46% yield). MS (ESI) m/z 417.99 (M+H). 1H NMR (400 MHz, chloroform-d) δ ppm 8.39-8.47 (2H, m), 8.22-8.27 (2H, m), 8.19 (1H, d, J=7.55 Hz), 7.93-8.03 (2H, m), 7.54-7.65 (2H, m), 6.13 (2H, br. s.), 4.04 (3H, s).

Workup

  1. additionA flask containing
  2. customwas flushed with nitrogen
  3. additionTHF (20 mL) was added
  4. temperaturethe mixture was heated
  5. temperatureat reflux under nitrogen for 2 hr
  6. additionThe mixture was diluted with EtOAc
  7. washwashed with water and brine
  8. dry with materialAfter drying with Na2SO4), the solvents
  9. customremoved
  10. additionthe residue was suspended in a mixture of 20% EtOAc in hexane
  11. filtrationFiltration

Sources & evidence

ORD record
ord-03e8afbbd0f547bc9150df1c8c7bc4b8
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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