Cesium carbonate → 3-Fluoro-3'-(trifluoromethyl)-(1,1'-biphenyl)-4-carboxylic acid

HRID 403321Notes

Reaction equation

HRID 403321 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[C:14]([O-:17])([O-])=[O:15].[Cs+].[Cs+].O1[CH2:25][CH2:24]OCC1>CCO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[CH:3]=[C:8]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=2)[CH:7]=[CH:24][C:25]=1[C:14]([OH:17])=[O:15]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 27343883-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 167687113-Fluoro-3'-(trifluoromethyl)-(1,1'-biphenyl)-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of compound 26a (75 mg, 0.345 mmol), compound 15b (80 mg, 0.42 mmol), and Cs2CO3 (282 mg, 0.864 mmol) in dioxane (9 mL) and EtOH (3 mL) was added Pd(dppf)Cl2 (0.0252 g, 0.0345 mmol). The reaction mixture was stirred at 80° C. for 3 h. After cooling, the solid was removed by filtration and washed with CH3OH. The filtrate was concentrated. The crude compound 26b was purified by reverse phase chromatography.

Workup

  1. temperatureAfter cooling
  2. customthe solid was removed by filtration
  3. washwashed with CH3OH
  4. concentrationThe filtrate was concentrated
  5. customThe crude compound 26b was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-e8a955a8958f43f2bd0711a79662d3a5
Source dataset
uspto-grants-2014_06
Patent number
US08748417B2

Reaction notes

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