Toluene → HCID 66604928, compound

HRID 2410662Notes

Reaction equation

HRID 2410662 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=2)=[C:4]([C:20]#[N:21])[CH:3]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:35][C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][C:41]=1[Cl:42]>CO.O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:35][C:36]1[CH:37]=[C:38]([C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9]3[CH:19]=[CH:18][C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:10]=3)=[C:4]([C:20]#[N:21])[CH:3]=2)[CH:39]=[CH:40][C:41]=1[Cl:42]

Participants

9

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343303,4-Dichlorobenzeneboronic acidHCID 66605156HCID 66605156, compound

Product 1

HCID 66604928HCID 66604928, compoundYield 70.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of ethyl 4-(4-bromo-2-cyanophenylamino)benzoate (6.33 g, 18.34 mmol), tetrakis(triphenylphosphine)palladium(0) (0.438 g, 0.379 mmol), toluene (60 mL), and 2 M aqueous sodium carbonate (20.81 mL, 41.6 mmol) under nitrogen were added a solution of 3,4-dichlorophenylboronic acid (4.76 g, 24.94 mmol) in MeOH (18 mL) at rt. The resulting reaction mixture was heated at reflux temperature for 4 h. The reaction mixture was cooled to room temperature and diluted with water (100 mL) and ethyl acetate (250 mL). The aqueous phase was extracted with ethyl acetate (100 ml ×2), and the combined organic phase was washed with water (100 ml ×2), diluted (5%) aqueous ammonia (100 mL), and brine (100 mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The crude material was suspended in dichloromethane and the solid was collected by filtration, and washed with DCM (5 ml ×2) to afford 5.33 g of ethyl 4-(3′,4′-dichloro-3-cyanobiphenyl-4-ylamino)benzoate. MS (ESI) m/z 411.0 (M+H). 1H NMR (CDCl3) δ ppm 8.04 (2H, d, J=8.55 Hz), 7.73 (1H, d, J=1.83 Hz), 7.58-7.66 (2H, m), 7.51 (1H, d, J=8.55 Hz), 7.46 (1H, d, J=8.85 Hz), 7.34 (1H, dd, J=8.24, 2.14 Hz), 7.20 (2H, d, J=8.55 Hz), 6.61 (1H, s), 4.37 (2H, q, J=7.12 Hz), 1.39 (3H, t, J=7.17 Hz).

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas heated
  3. temperatureat reflux temperature for 4 h
  4. extractionThe aqueous phase was extracted with ethyl acetate (100 ml ×2)
  5. washthe combined organic phase was washed with water (100 ml ×2)
  6. additiondiluted (5%) aqueous ammonia (100 mL), and brine (100 mL)
  7. dry with materialThe organic phase was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. filtrationthe solid was collected by filtration
  11. washwashed with DCM (5 ml ×2)

Sources & evidence

ORD record
ord-ee403eff673442dc901f4436fc4a1556
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…