Lithium Hydroxide → 7-Methoxy-1H-indazole-5-carboxylic acid

HRID 1880363Notes

Reaction equation

HRID 1880363 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]([O:20]CC)=[O:19])[CH:6]=[C:7]2[C:11]=1[N:10](C1CCCCO1)[N:9]=[CH:8]2.[Li+].[OH-]>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:18]([OH:20])=[O:19])[CH:6]=[C:7]2[C:11]=1[NH:10][N:9]=[CH:8]2

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

Product 1

HCID 669206267-Methoxy-1H-indazole-5-carboxylic acidYield 75.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (980 mg, 4.45 mmol) in THF (10 mL), water (10 mL) and LiOH (560 mg, 13.4 mmol) was heated at 40° C. for 3 hours and then stirred at room temperature overnight. The reaction was not complete so the mixture was heated to 45° C. and heated overnight. The mixture was then concentrated to dryness, acidified to pH 6 with conc. HCl and partitioned between EtOAc and water. The resultant solids were collected by vacuum filtration, rinsed with EtOAc and dried under high vacuum to afford a white solid. The organic layer was washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated to provide an off-white solid. Both batches of white solid were combined to afford the title compound (642 mg, 75%).

Workup

  1. temperaturewas heated to 45° C.
  2. temperatureheated overnight
  3. concentrationThe mixture was then concentrated to dryness
  4. custompartitioned between EtOAc and water
  5. filtrationThe resultant solids were collected by vacuum filtration
  6. washrinsed with EtOAc
  7. customdried under high vacuum
  8. customto afford a white solid
  9. washThe organic layer was washed with saturated aqueous NaCl
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto provide an off-white solid

Sources & evidence

ORD record
ord-99ee304eb1184ff98ad23e17eeba3732
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

Loading…