Hydrochloric Acid → Benzyl 1-benzyl-1H-indazole-3-carboxylate

HRID 343094Notes

Reaction equation

HRID 343094 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[N:2]1.C([O-])([O-])=O.[K+].[K+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>CN(C=O)C>[CH2:19]([O:11][C:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:1]([CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[N:2]=1)=[O:12])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 78250Indazole-3-carboxylic acid

Product 1

HCID 10712329Benzyl 1-benzyl-1H-indazole-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 750 mg (4.62 mmol) of 1H-Indazole-3-carboxylic acid (Snyder, H. R.; Thompson, C. B.; Hinman, R. L. J. Am. Chem. Soc. 1952, 74, 2009) in 20 mL of DMF is added 1.92 g (13.86 mmol, 3.0 equiv) of K2CO3, followed by 1.43 mL of benzyl bromide. The reaction mixture is stirred 15 min at RT then heated at 60° C. for 16 h. The reaction is cooled to RT, poured into 100 mL 1N HCl, and extracted with EtOAc (2×100 mL). The organic layers are washed with H2O (2×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using a gradient elution of hexane/EtOAc 20/1 to 2/1 afforded 735 mg of the title compound as a yellow oil which later solidified: 1H NMR (CDCl3, 300 MHz) δ8.20 (d, 1H), 7.55 (d, 2H), 7.40-7.18 (m, 11H), 5.70 (s, 2H), 5.57 (s, 2H); Rf =0.15 in hexane/EtOAc 10/1.

Workup

  1. temperaturethen heated at 60° C. for 16 h
  2. temperatureThe reaction is cooled to RT
  3. extractionextracted with EtOAc (2×100 mL)
  4. washThe organic layers are washed with H2O (2×100 mL)
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customPurification of the crude material by silica gel flash column chromatography
  8. washa gradient elution of hexane/EtOAc 20/1 to 2/1

Sources & evidence

ORD record
ord-847e1346b1a045e09067198c744e4e6e
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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