Toluene → Methyl 2-cyclopropyl-6-fluorobenzoate

HRID 1190927Notes

Reaction equation

HRID 1190927 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:13]1(B(O)O)[CH2:15][CH2:14]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C)C=CC=CC=1>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.O>[CH:13]1([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:3]=2[C:4]([O:6][CH3:7])=[O:5])[CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 12192163Methyl 2-bromo-6-fluorobenzoate

Product 1

HCID 67997313Methyl 2-cyclopropyl-6-fluorobenzoateYield 99%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

Methyl 2-bromo-6-fluorobenzoate (2, 11.29 g, 48.5 mmol), cyclopropylboronic acid (6.24 g, 72.7 mmol), K3PO4 (30.85 g, 145.4 mmol) and Pd(PPh3)4 (2.80 g, 2.4 mmol) were mixed under argon in a degassed mixture of toluene and water (20:1, 160 mL). The resulting brown suspension was heated at reflux for 2.5 h, cooled, filtered through Celite, and evaporated. The residue was partitioned between ethyl acetate (150 mL) and brine (150 mL). The layers were separated and organic layer was dried over magnesium sulfate and evaporated. The oily residue was suspended in hexane and the solid was removed by filtration. Evaporation of the filtrate afforded the title compound (9.30 g, 47.9 mmol, 99%) as a light brown oil.

Workup

  1. temperatureThe resulting brown suspension was heated
  2. temperatureat reflux for 2.5 h
  3. temperaturecooled
  4. filtrationfiltered through Celite
  5. customevaporated
  6. customThe residue was partitioned between ethyl acetate (150 mL) and brine (150 mL)
  7. customThe layers were separated
  8. dry with materialorganic layer was dried over magnesium sulfate
  9. customevaporated
  10. customthe solid was removed by filtration
  11. customEvaporation of the filtrate

Sources & evidence

ORD record
ord-6e7fe67353114868bcf4e91685dc2f3a
Source dataset
uspto-grants-2014_03
Patent number
US08680099B2

Reaction notes

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