Sodium Carbonate → HCID 136365471, compound

HRID 2283638Notes

Reaction equation

HRID 2283638 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6](B(O)O)[CH:7]=1.Br[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH2:19])[CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C(OCC)(=O)C.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>[NH2:19][C:15]1[CH:14]=[C:13]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[OH:11])[CH:18]=[CH:17][N:16]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 6932822-Amino-4-bromopyridineHCID 37724765-Fluoro-2-hydroxyphenylboronic acid

Product 1

HCID 136365471HCID 136365471, compoundYield 86.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Argon was bubbled through a suspension of (5-fluoro-2-hydroxyphenyl)boronic acid (55.0 mg, 0.35 mmol), 4-bromopyridin-2-amine (67.1 mg, 0.39 mmol) and sodium carbonate (0.15 g, 1.4 mmol) in 1,4-dioxane (0.9 mL) and water (0.3 mL) for 5 minutes then tetrakis(triphenylphosphine)palladium(0) (41 mg, 0.04 mmol) was added. The resulting mixture was heated at 85° C. for 22 hours then cooled to ambient temperature and diluted with ethyl acetate and water. The layers were separated and the aqueous layer extracted with ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by automated silica gel flash chromatography (0% to 100% ethyl acetate in hexanes gradient elution) to afford the title compound as a light tan solid (62 mg).

Workup

  1. temperaturethen cooled to ambient temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with ethyl acetate
  4. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by automated silica gel flash chromatography (0% to 100% ethyl acetate in hexanes gradient elution)

Sources & evidence

ORD record
ord-b0e5e11173114447a0560166964c268f
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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