Hydrochloric Acid → 1H-indazol-1-ylacetic acid

HRID 1081974Notes

Reaction equation

HRID 1081974 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1.C[O-].[Na+].Br[CH2:14][C:15]([OH:17])=[O:16].Cl>CO.C(OCC)(=O)C>[C:15]([CH2:14][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[N:2]1)([OH:17])=[O:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6227Bromoacetic Acid2×HCID 92211H-IndazoleHCID 10942334Sodium Methoxide2×

Product 1

HCID 64228301H-indazol-1-ylacetic acidYield 33%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of indazole (1.0 g, 8.3 mM) in methanol (10 μl) are added 28% solution of sodium methoxide in methanol (3.53 ml, 18.26 mmole) and bromoacetic acid (1.41 g, 9.96 mmole), and the mixture is heated to reflux for 2 hr. After addition of the same amount of sodium methoxide and bromoacetic acid, the mixture is heated to reflux for another 1 hr. This procedures of addition are repeated two more times and the mixture is cooled to 0° C. After addition of ethyl acetate, the mixture is adjusted to pH 5 with 1N HCl. The organic layer is taken and the aqueous layer extracted with ethyl acetate. Each organic solution is washed with a brine, dried over anhydrous magnesium sulfate and concentrated. The residue, when purified with column chromatography (SiO2, ethyl acetate→ethyl acetate/acetic acid/water, (40:1:1)→(30:1:1)→(8:1:1)), gives 1-carboxymethylindazole (487 mg, yield 33%).

Workup

  1. temperaturethe mixture is heated
  2. temperatureto reflux for 2 hr
  3. temperaturethe mixture is heated
  4. temperatureto reflux for another 1 hr
  5. additionThis procedures of addition
  6. extractionthe aqueous layer extracted with ethyl acetate
  7. washEach organic solution is washed with a brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated
  10. customThe residue, when purified with column chromatography (SiO2, ethyl acetate→ethyl acetate/acetic acid/water, (40:1:1)→(30:1:1)→(8:1:1))

Sources & evidence

ORD record
ord-1df1fda3c7664c299a638e5ea0a87ab8
Source dataset
uspto-grants-1996_12
Patent number
US05587505

Reaction notes

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