Sodium Carbonate → 3-Chloro-5-fluoro[1,1′-biphenyl]-4-amine

HRID 1270715Notes

Reaction equation

HRID 1270715 reaction equation
[F:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[C:5]([Cl:10])[C:3]=1[NH2:4].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:8]=[C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[C:5]([Cl:10])[C:3]=1[NH2:4]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 18451511HCID 18451511, compound

Product 1

HCID 184515133-Chloro-5-fluoro[1,1′-biphenyl]-4-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
100 °C

Procedure

2-Fluoro-4-iodo-6-chloroaniline (8.0 g, 36.0 mmol) is dissolved in DMF (110 mL) and treated with 2.8 equivalents of phenylboronic acid (10.0 g, 82 mmol), and a catalytic amount of tetrakistriphenylphosphine palladium(0) (3.0 g, 2.6 mmol) as a solution in DMF (20 mL). Sodium carbonate (30 mL of 2 M aqueous solution) is added and the reaction mixture stirred and heated to 100° C. for 24 hours. After cooling to room temperature most of the DMF is removed by rotary evaporator under high vacuum. The residual brown oil is partitioned between Et2O (300 mL) and water (150 mL). The organic layer is washed with brine, dried (MgSO4) and concentrated by rotary evaporator. The residual oil is purified by flash chromatography (9:1 hexanes/EtOAc) to give 2-fluoro-4-phenyl-6-chloroaniline (m.p. 105–107° C.).

Workup

  1. customis removed by rotary evaporator under high vacuum
  2. customThe residual brown oil is partitioned between Et2O (300 mL) and water (150 mL)
  3. washThe organic layer is washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated by rotary evaporator
  6. customThe residual oil is purified by flash chromatography (9:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-eba064c4d488485994f965832c648679
Source dataset
uspto-grants-2007_04
Patent number
US07202364B2

Reaction notes

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