Water → 2-(Trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acid

HRID 423318Notes

Reaction equation

HRID 423318 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[C:7]([C:9](N)=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[OH-:20].[K+].O>C(O)C>[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[C:7]([C:9]([OH:20])=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 666771582-(Trifluoromethyl)-4-biphenylcarboxamide

Product 1

HCID 463151912-(Trifluoromethyl)-[1,1'-biphenyl]-4-carboxylic acidYield 47.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

The reaction was split into 4, using a quarter of the reagents in each: to a mixture of 4-bromo-3-(trifluoromethyl)benzonitrile (4 g, 16.00 mmol), phenylboronic acid (3.90 g, 32.0 mmol) and potassium carbonate (6.63 g, 48.0 mmol) in N,N-dimethylformamide (DMF) (64 ml) was added palladium tetrakistriphenylphosphine(0) (1.849 g, 1.600 mmol). Each reaction was heated in the microwave at 150° C. for 30 min. The combined reaction mixtures were filtered through celite, washed with ethyl acetate and the solvent removed in vacuo. The residue was partitioned between ethyl acetate (100 mL) and water (100 mL) and the organic phase washed with sodium bicarbonate solution (100 mL). The organic phase was dried (MgSO4), filtered and the solvent removed in vacuo. The brown oil was triturated with dichloromethane and filtered to give a pale yellow solid, 2-(trifluoromethyl)-4-biphenylcarboxamide (2.47 g) which was used without further purification. To 2-(trifluoromethyl)-4-biphenylcarboxamide (2 g, 7.54 mmol) in ethanol (80 ml) was added potassium hydroxide (4.23 g, 75 mmol) and water and the mixture heated to 90° C. for 18 h. The reaction mixture was concentrated in vacuo and the residue partitioned between dichloromethane (100 mL) and 2M HCl (100 mL). The organic phase was isolated and dried (phase separator) and the solvent removed in vacuo to give the crude product. Purification using the Biotage Horizon, reverse phase cartridge, eluting 5-100% MeCN in water to give an off-white solid the title compound (960 mg) (N2123-46-A5). MS (ES): C14H6F3O2 requires 266; found 265 (M−H+).

Workup

  1. customwas used without further purification
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue partitioned between dichloromethane (100 mL) and 2M HCl (100 mL)
  4. customThe organic phase was isolated
  5. customdried (phase separator)
  6. customthe solvent removed in vacuo
  7. customto give the crude product
  8. customPurification
  9. washeluting 5-100% MeCN in water

Sources & evidence

ORD record
ord-f899ce2a0a0b40599f9bd96c84336f0d
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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