Trifluoroacetic acid → HCID 68688990, compound

HRID 1175215Notes

Reaction equation

HRID 1175215 reaction equation
Br[C:2]1[C:3]([F:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C([Sn](CCCC)(CCCC)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1)CCC.C(O)(C(F)(F)F)=O>[Ag]=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.CN(C=O)C>[F:12][C:3]1[C:2]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([OH:7])=[O:6].[F:12][C:3]1[C:2]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6]

Participants

8

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 6077842-(Tributylstannyl)pyridineHCID 21584505Methyl 3-bromo-2-fluorobenzoate

Product 2

HCID 68687070HCID 68687070, compoundYield 17%HCID 68688990HCID 68688990, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 92152Silver(II) oxideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

In a 150 mL round bottom flask was combined methyl 3-bromo-2-fluorobenzoate (1.47 g, 6.3 mmol), DMF (10 mL), silver oxide (0.79 g, 6.4 mmol), 2-(tributylstannyl)pyridine (2.40 ml, 7.2 mmol), and dichlorobis(triphenylphosphine)-palladium (II) (0.23 g, 0.33 mmol) and the mixture was stirred at 100° C. to about 72 h. Monitoring the reaction by LC-MS revealed two products, the ester and the hydrolyzed product. The reaction was cooled, filtered through a pad of celite and the celite was washed with EtOAc. The filtrate was concentrated in vacuo and taken up in a small amount of DMF. The solution was purified by reverse-phase preparative HPLC on a Phenomenex Luna column (10 micron, C18, 100 Å, 150×50 mm) eluting at 45 ml/min with an linear gradient of 10% (v/v) to 100% MeCN (0.1% v/v TFA) in water (0.1% TFA) over 10 minutes to give 2-fluoro-3-(pyridine-2-yl)benzoic acid (0.24 g, 0.72 mmol, 23% yield) as a light red-colored TFA salt and methyl 2-fluoro-3-(pyridine-2-yl)benzoate (0.19 g, 0.55 mmol, 17% yield) as a golden syrup-colored TFA salt.

Workup

  1. customIn a 150 mL round bottom flask was combined
  2. customMonitoring the reaction by LC-MS
  3. temperatureThe reaction was cooled
  4. filtrationfiltered through a pad of celite
  5. washthe celite was washed with EtOAc
  6. concentrationThe filtrate was concentrated in vacuo
  7. customThe solution was purified by reverse-phase preparative HPLC on a Phenomenex Luna column (10 micron, C18, 100 Å, 150×50 mm)
  8. washeluting at 45 ml/min with an linear gradient of 10% (v/v) to 100% MeCN (0.1% v/v TFA) in water (0.1% TFA) over 10 minutes

Sources & evidence

ORD record
ord-f44e93f7190f4b1b9a8396872c2f9359
Source dataset
uspto-grants-2010_11
Patent number
US07838676B2

Reaction notes

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