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

HRID 338461Notes

Reaction equation

HRID 338461 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. 1N 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-afec4fb6a9b64deeaddf85a7ba2f1d3d
Source dataset
uspto-grants-2014_11
Patent number
US08889730B2

Reaction notes

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