4-Fluoro-1H-indazole-5-carboxylic acid synthesis

Yield:-

Reaction Conditions:

with sulfuric acid;water;acetic acid at 110; for 4 h;

Steps:

86
To 1.65 g of 4-fluoro-1H-indazole-5-carbonitrile obtained by Production example 85, 8 mL of glacial acetic acid, 8 mL of water and 16 mL of concentrated sulfuric acid were added and stirred at 110°C for 4 hours. After allowing the reaction solution to cool, 150 mL of ice water was added, and the precipitated carboxylic acid was collected by filtration. Under ice cooling, to a solution of the obtained carboxylic acid in N,N-dimethylformamide 12 mL-tetrahydrofuran 40 mL, a solution containing excess diazomethane in diethyl ether was added, and stirred at this temperature for 45 minutes. After distilling off the solvent under reduced pressure, the residue was dissolved in 100 mL of ethyl acetate, washed successively with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated, to afford 1.98 g of the title compound as bright yellow crystals.1H-NMR ( 400 MHz, DMSO-D6 ) δ 3.87 ( 3H, s ), 7.45 ( 1H, d, J = 8.8 Hz ), 7.82 ( 1H, dd, J = 6.8, 8.8 Hz ), 8.36 ( 1H, s ), 13.70 ( 1H, s )

References:

Eisai Co., Ltd. EP1510516, 2005, A1 Location in patent:Page/Page column 86