Potassium Phosphate, Tribasic → Methyl 3-bromo-5-(5-methylpyridin-2-yl)benzoate

HRID 418388Notes

Reaction equation

HRID 418388 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[CH3:9][O:10][C:11](=[O:28])[C:12]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[C:14]([Br:27])[CH:13]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:9][O:10][C:11](=[O:28])[C:12]1[CH:17]=[C:16]([C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=2)[CH:15]=[C:14]([Br:27])[CH:13]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 5642162-Bromo-5-methylpyridineHCID 53436914Methyl 3-bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)benzoate

Product 1

HCID 59599704Methyl 3-bromo-5-(5-methylpyridin-2-yl)benzoateYield 51.2%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-bromo-5-methyl-pyridine (10.27 g, 59.68 mmol) and palladium tetrakis(triphenylphosphine) (1.88 g, 1.65 mmol) in 300 mL DME was stirred at 60° C. under nitrogen for 30 minutes. To this mixture was added 3-bromo-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (18.5 g, 54.25 mmol), followed by K3PO4 23.03 g, 108.5 mmol) in 40 mL water. The mixture was refluxed for eight hours, then cooled to room temperature and partitioned between water and EtOAc. The combined organic layers were washed with water, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified via flash chromatography (5:1 EtOAc/hexanes) to give 8.5 g of 3-bromo-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester, MS (M+H)=306.

Workup

  1. temperatureThe mixture was refluxed for eight hours
  2. temperaturecooled to room temperature
  3. custompartitioned between water and EtOAc
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified via flash chromatography (5:1 EtOAc/hexanes)

Sources & evidence

ORD record
ord-42ce149b81f445bc9a76616282ad5f68
Source dataset
uspto-grants-2012_01
Patent number
US08093275B2

Reaction notes

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