Lithium Hydroxide → 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acid

HRID 880948Notes

Reaction equation

HRID 880948 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]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[N:9]=[CH:8]2.[OH-].[Li+]>O1CCCC1>[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[N:10]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[N:9]=[CH:8]2

Participants

4

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

Product 1

HCID 674914847-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylic acidYield 92.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (102 mg, 0.33 mmol) in tetrahydrofuran (2 mL) was added 1 N aqueous lithium hydroxide (0.67 mL, 0.67 mmol). The reaction was stirred at room temperature overnight. LCMS showed the reaction to be incomplete. Additional lithium hydroxide (0.35 mL, 2 M, 0.7 mmol) was added and the reaction was heated to 40° C. for 1 hour. The reaction was then left stirring at room temperature for 70 hours. The tetrahydrofuran was removed in vacuo and the residue was acidified to pH=4 with 1 N aqueous hydrochloric acid. The solution was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the title compound (84 mg, 91%) as a solid. (M+1-THP) 193.2; 1H NMR (400 MHz, CDCl3, δ): 8.18 (d, J=1.37 Hz, 1H), 8.12 (s, 1H), 7.46 (d, J=1.17 Hz, 1H), 6.26 (dd, J=10.15, 2.54 Hz, 1H), 4.07-4.12 (m, 1H), 4.06 (s, 3H), 3.65-3.81 (m, 1H), 2.54-2.72 (m, 1H), 2.10-2.22 (m, 1H), 2.01-2.10 (m, 1H), 1.71-1.85 (m, 2H), 1.57-1.67 (m, 1H).

Workup

  1. customthe reaction
  2. temperaturethe reaction was heated to 40° C. for 1 hour
  3. waitThe reaction was then left
  4. stirringstirring at room temperature for 70 hours
  5. customThe tetrahydrofuran was removed in vacuo
  6. extractionThe solution was extracted with ethyl acetate (3×)
  7. washThe combined organics were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-7ca90da7cac24058b33bbc835465f973
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

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