Sodium Carbonate → 4-Amino-3'-chloro-biphenyl-3-carbonitrile

HRID 277841Notes

Reaction equation

HRID 277841 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:3]=1[C:4]#[N:5].[Cl:11][C:12]1[CH:13]=[C:14](B(O)O)[CH:15]=[CH:16][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[CH:9]=[CH:8][C:7]([C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:11])[CH:17]=2)=[CH:6][C:3]=1[C:4]#[N:5]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 4297402-Amino-5-bromobenzonitrileHCID 2734323(3-Chlorophenyl)boronic acid

Product 1

HCID 97945754-Amino-3'-chloro-biphenyl-3-carbonitrileYield 87%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-amino-5-bromobenzonitrile (10 g, 50 mmol), 3-chlorophenyl boronic acid (9.5 g, 60 mmol), tetrakis(triphenylphosphine)-palladium(0) (3.5 g, 3 mmol), and sodium carbonate (13 g, 120 mmol) in a mixture of DME and water (100 mL/25 mL) was degassed to remove the oxygen and then heated to 85° C. under a blanket of nitrogen for 5 hours. The reaction mixture was cooled to ambient temperature and quenched with a saturated aqueous ammonium chloride solution (80 mL). Ethyl acetate (200 mL) was added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/4:1) to afford 4-amino-3′-chloro-biphenyl-3-carbonitrile as an off-white solid (8 g, 87%): mp 118-119° C.; 1H-NMR (DMSO-d6) δ 7.80 (d, 1H, J=2.3 Hz), 7.65-7.72 (m, 2H), 7.57 (d, 1H, J=8.0 Hz), 7.42 (t, 1H, J=7.9 Hz), 7.31 (m, 1H), 6.87 (d, 1H, J=8.7 Hz), 6.29 (br, 2H); Anal. Calc. For C13H9ClN2: C, 68.28, H. 3.97, N, 12.25. Found: C, 67.68, H, 4.06, N, 11.89.

Workup

  1. customwas degassed
  2. customto remove the oxygen
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. customquenched with a saturated aqueous ammonium chloride solution (80 mL)
  5. additionEthyl acetate (200 mL) was added
  6. customthe organic layer was separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (3×40 mL)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried with MgSO4
  10. customThe solvent was removed in vacuo
  11. customthe residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/4:1)

Sources & evidence

ORD record
ord-fa0e369105694122b8b550d0d3fac306
Source dataset
uspto-grants-2002_03
Patent number
US06358948B1

Reaction notes

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