Hydrochloric Acid → 5-(2-Fluoro-4-methoxyphenyl)-6-methyl-1H-indazole-3-carboxylic acid

HRID 1054804Notes

Reaction equation

HRID 1054804 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][C:11]([CH3:24])=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=3[F:23])[CH:13]=2)[NH:8][N:7]=1)=[O:5])C.[Li+].[OH-].Cl>C1COCC1.O>[F:23][C:16]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:15]=1[C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[CH3:24])[NH:8][N:7]=[C:6]2[C:4]([OH:5])=[O:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86698795Ethyl 5-(2-fluoro-4-methoxyphenyl)-6-methyl-1H-indazole-3-carboxylate

Product 1

HCID 866987965-(2-Fluoro-4-methoxyphenyl)-6-methyl-1H-indazole-3-carboxylic acidYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(2-fluoro-4-methoxyphenyl)-6-methyl-1H-indazole-3-carboxylic acid ethyl ester (292 mg, 0.89 mmol) in THF (4 mL) was added a solution of LiOH (298.0 mg, 12.25 mmol) in water (2 mL). The reaction mixture was heated to reflux for 9 hours, and stirred at room temperature for an additional 48 hours. 1 N HCl solution was added to acidify the solution to pH 2. White solid formed, which was collected with filtration and dried in a vacuum oven at 50° C. for 4 hours to give the title compound (240 mg, 90% yield) as a solid. MS (ES+) 301.2 (M+H)+. 1H NMR (500 MHz, CD3OD) δ 7.92 (s, 1H), 7.51 (s, 1H), 7.22 (dd, J=8.70, 8.70 Hz, 1H), 6.87 (dd, J=8.42, 2.56 Hz, 1H), 6.81 (dd, J=11.59, 2.56 Hz, 1H), 3.88 (s, 3H), 2.30 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 9 hours
  3. customWhite solid formed
  4. filtrationwhich was collected with filtration
  5. customdried in a vacuum oven at 50° C. for 4 hours

Sources & evidence

ORD record
ord-549c64b6acb04e6ca125df0a668c234e
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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