Ethyl Acetate → 2-(5-Bromo-2-methoxy-pyridin-3-yl)-5-trifluoromethyl-benzaldehyde

HRID 554614Notes

Reaction equation

HRID 554614 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:10]=2[CH:11]=[O:12])O1.Br[C:23]1[C:24]([O:30][CH3:31])=[N:25][CH:26]=[C:27]([Br:29])[CH:28]=1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>COCCOC.O.[Cl-].[Na+].O.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>[Br:29][C:27]1[CH:28]=[C:23]([C:9]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][C:10]=2[CH:11]=[O:12])[C:24]([O:30][CH3:31])=[N:25][CH:26]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 135677523,5-Dibromo-2-methoxypyridineHCID 866405342-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzaldehyde

Product 1

HCID 866405372-(5-Bromo-2-methoxy-pyridin-3-yl)-5-trifluoromethyl-benzaldehyde

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

2-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-benzaldehyde (1.59 g, 4.4 mmol), 3,5-dibromo-2-methoxy-pyridine (1.19 g, 4.4 mmol), and potassium carbonate (2.17 g, 15.6 mmol) were combined in DME (13 mL) and H2O (6 mL). The solution was purged with N2 for 30 minutes, and dichlorobis(triphenylphosphine)palladium(II) (0.156 g, 0.22 mmol) was added. The reaction was stirred at 85° C. overnight, and then cooled to room temperature and worked-up with EtOAc and brine. The combined organic layers were dried over MgSO4, filtered, and concentrated, and the residue was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give 2-(5-bromo-2-methoxy-pyridin-3-yl)-5-trifluoromethyl-benzaldehyde, which was repurified by preparative HPLC.

Workup

  1. customThe solution was purged with N2 for 30 minutes
  2. temperaturecooled to room temperature
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe residue was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-85432fc2f6f240acabdb14bcdaab98d6
Source dataset
uspto-grants-2011_11
Patent number
US08049015B2

Reaction notes

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