Water → Methyl 2-chloro-2'-(trifluoromethyl)biphenyl-4-carboxylate

HRID 2404335Notes

Reaction equation

HRID 2404335 reaction equation
B([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[Cl:14])(O)O.Br[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:24])[F:23].[F-].[Cs+].O>O1CCOCC1.CC(OC)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][C:5]1[CH:6]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[CH:12]=[CH:13][C:4]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:24])[F:23]

Participants

8

Reactant 4

HCID 962WaterHCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 25953Cesium fluorideHCID 221712912-Chloro-4-(methoxycarbonyl)benzeneboronic acid

Product 1

HCID 66718347Methyl 2-chloro-2'-(trifluoromethyl)biphenyl-4-carboxylate

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 4-borono-3-chlorobenzoate (Combi-Blocks BB-3530, 1.5 g, 7.0 mmol), 2-bromobenzotrifluoride (1.9 g, 8.4 mmol), cesium fluoride (3.2 g; 21.0 mmol) and bis(triphenylphosphine)palladium(II) chloride (98 mg, 0.14 mmol) was prepared in dioxane (15 mL) and water (7.5 mL) under nitrogen atmosphere, and then heated at 90° C. for 30 minutes. The reaction mixture was diluted with MTBE (30 mL) and washed with water and brine. The aqueous layers were extracted with MTBE (30 mL). The combined organic layers were dried (MgSO4) and concentrated under vacuum. After two purifications by flash chromatography (silica, heptane/DCM, then heptane/EtOAc), the title compound was obtained as a yellow oil. HPLC (Method A) Rt 5.3 min (Purity: 99.7%).

Workup

  1. washwashed with water and brine
  2. extractionThe aqueous layers were extracted with MTBE (30 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-33f9a1668d9d4ee08d656e807ae48687
Source dataset
uspto-grants-2014_08
Patent number
US08802704B2

Reaction notes

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