(Pyridin-4-yl)boronic acid → HCID 18470704, compound

HRID 2228616Notes

Reaction equation

HRID 2228616 reaction equation
[C:1]([C:4]1[C:5]([CH3:16])=[C:6](Br)[NH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:3])[CH3:2].[N:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1>COCCOC.C([O-])(O)=O.[Na+].C(OCC)(=O)C.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>[C:1]([C:4]1[C:5]([CH3:16])=[C:6]([C:20]2[CH:21]=[CH:22][N:17]=[CH:18][CH:19]=2)[NH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 2

HCID 2734379(Pyridin-4-yl)boronic acidHCID 18470770HCID 18470770, compound

Product 1

HCID 18470704HCID 18470704, compoundYield 30.4%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred suspension of 4-acetyl-2-bromo-3-methyl-5-phenyl-1H-pyrrole (139 mg, 0.50 mmol), 4-pyridylboronic acid (307 mg, 2.5 mmol) in DME (1.5 mL) and saturated aqueous NaHCO3 (0.50 mL) was added Pd(PPh3)2Cl2 (70 mg, 0.10 mmol) under nitrogen. The mixture was heated under reflux for 12 hours. After cooling, the mixture was diluted with ethyl acetate (5 mL) and water (10 mL). The organic layer was separated, and then the aqueous layer was extracted with ethyl acetate (5 mL×2). The combined organic layers were extracted with 1M aqueous HCl (3 mL×2). The combined aqueous layes were neutralized by the addition of 10% aqueous KOH until being pH=8. The whole was extracted with CH2Cl2 (10 mL×3), the combined organic layers were dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography eluting with hexane-ethyl acetate (1:2→EtOAc only) to provide the title product (42 mg, 30% yield) as a colorless solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 12 hours
  3. temperatureAfter cooling
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (5 mL×2)
  6. extractionThe combined organic layers were extracted with 1M aqueous HCl (3 mL×2)
  7. additionThe combined aqueous layes were neutralized by the addition of 10% aqueous KOH
  8. extractionThe whole was extracted with CH2Cl2 (10 mL×3)
  9. dry with materialthe combined organic layers were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography
  12. washeluting with hexane-ethyl acetate (1:2→EtOAc only)

Sources & evidence

ORD record
ord-a48f6a47b0dd40f6ba564e21ead734fb
Source dataset
uspto-grants-2002_07
Patent number
US06417202B1

Reaction notes

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