Citric Acid → Methyl 1H-indazole-5-carboxylate

HRID 1880368Notes

Reaction equation

HRID 1880368 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2C.C[C:13]([O-:15])=[O:14].[Na+].[CH3:17]N(C=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.Cl[Pd]Cl.O.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.[Fe+2]>[CH3:17][O:15][C:13]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2)=[O:14]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 6228DimethylformamideHCID 517045Sodium AcetateHCID 178434225HCID 178434225, compound

Product 1

HCID 22260640Methyl 1H-indazole-5-carboxylateYield 80%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 24290Palladium ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromo-3-methyl-1H-indazole (10 g, 47.6 mmol) in MeOH (160 mL), PdCl2.dppf (5.57 g, 7.62 mmol), NaOAc (11.7 g, 142.85 mmol) and DMF (5 mL) were added and degassed (using N2 gas 3-times). The mixture was sealed, charged with CO gas (60 psi) and heated at 80° C. for 20 hours. The reaction mixture was concentrated to obtain a residue, which was diluted with water (100 mL), acidified with 10% aqueous citric acid and extracted using ethyl acetate (3×200 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to afford 1H-indazole-5-carboxylic acid methyl ester (7.23 g, 80%) as a solid. 1H NMR (CDCl3): δ 9.6-10.2 (br, 1H), 8.4-8.6 (s, 1H), 8.0-8.2 (d, 1H), 7.4-7.5 (d, 1H), 3.9-4.05 (s, 3H), 2.55-2.7 (s, 3H).

Workup

  1. customdegassed (using N2 gas 3-times)
  2. customThe mixture was sealed
  3. additioncharged with CO gas (60 psi)
  4. concentrationThe reaction mixture was concentrated
  5. customto obtain a residue, which
  6. extractionextracted
  7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-05adbb388f4f43558c0bc7326d786ce0
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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