Hydrochloric Acid → 2-Fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid

HRID 1771617Notes

Reaction equation

HRID 1771617 reaction equation
Br[C:2]1[C:3]([F:12])=[C:4]([CH:8]=[C:9]([CH3:11])[CH:10]=1)[C:5]([OH:7])=[O:6].[F:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+].Cl>C(#N)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:12][C:3]1[C:2]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([F:13])[CH:19]=2)=[CH:10][C:9]([CH3:11])=[CH:8][C:4]=1[C:5]([OH:7])=[O:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27339863-Fluorophenylboronic acidHCID 125134713-Bromo-2-fluoro-5-methylbenzoic acid

Product 1

HCID 894435072-Fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acidYield 75%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-bromo-2-fluoro-5-methyl-benzoic acid (400 mg, 1.7 mmol, 1.0 eq), (3-fluorophenyl)boronic acid (720 mg, 5.2 mmol, 3.0 eq), K2CO3 (356 mg, 2.6 mmol, 1.5 eq) and Pd(PPh3)4 (396.0 mg, 0.40 mmol, 0.2 eq) in acetonitrile (5 mL) and H2O (4 mL) was heated at reflux overnight. The reaction was acidified to pH 3 by addition of 1M HCl and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound as a solid (160 mg, 75%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. extractionextracted with EtOAc
  4. washThe combined organic extracts were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by chromatography (EtOAc:petroleum ether, 0:1 to 1:4)

Sources & evidence

ORD record
ord-19e6800bfa664814815290fed911bfe5
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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