Water → 5-(4-Fluoro-3-formylphenyl)-indazole-1-carboxylic acid tert-butyl ester

HRID 1435558Notes

Reaction equation

HRID 1435558 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:18][C:19]1[CH:26]=[C:25](C2OC(C)(C)C(C)(C)O2)[CH:24]=[CH:23][C:20]=1[CH:21]=[O:22].C(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:24]3[CH:25]=[CH:26][C:19]([F:18])=[C:20]([CH:21]=[O:22])[CH:23]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 962WaterHCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 22832025tert-Butyl 5-bromo-1H-indazole-1-carboxylateHCID 86620564HCID 86620564, compound

Product 1

HCID 866164695-(4-Fluoro-3-formylphenyl)-indazole-1-carboxylic acid tert-butyl esterYield 71.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-bromo-indazole-1-carboxylic acid tert-butyl ester (3.37 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-[1,3] dioxolan-2-yl)-benzaldehyde (1.01 g, 4.04 mmol)) PdCl2(dppf).DCM (27 mg, 0.03 mmol) in 16 mL of dioxane was degassed (evacuate in vacuo and pressurize with argon, three times); cesium carbonate in water (2M, 6.73 mL, 13.46 mmol) was added and the mixture degassed three more times as described above. The resulting mixture was heated at 85° C. for 6 h, then it was allowed to cool to room temperature and left overnight. The mixture was diluted with dichloromethane and washed with brine. The aqueous phase was extracted with dichloromethane and the combined organic phases were washed with brine, dried over MgSO4, filtered and evaporated to give crude product. Chromatography on silica gel (elution with diethyl ether/heptane) gave 820 mg of the title compound.

Workup

  1. custom(evacuate in vacuo and pressurize with argon, three times)
  2. customthe mixture degassed three more times
  3. temperatureto cool to room temperature
  4. additionThe mixture was diluted with dichloromethane
  5. washwashed with brine
  6. extractionThe aqueous phase was extracted with dichloromethane
  7. washthe combined organic phases were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customto give crude product

Sources & evidence

ORD record
ord-bc21cd5fa5dd467093117d3c4ed36577
Source dataset
uspto-grants-2009_11
Patent number
US07618650B2

Reaction notes

Loading…