The general procedure for the synthesis of 5-fluoroindazole-3-carboxylic acid from 5-fluoroindigo is as follows: first, sodium hydroxide (1.24 g, 0.031 mol, 1.03 eq.) was dissolved in water (19 mL) and heated to 50 °C, then 5-fluoroindigo (5 g, 0.03 mol, 1 eq.) was added. 5 minutes later, the resulting deep red solution was cooled to 0 °C, followed by the slow addition of a pre-cooled sodium nitrite (2.07 g, 0.03 mol, 1 eq.) solution in water (10 mL). Immediately thereafter, the cooled 95% sulfuric acid (3.12 mL, 0.06 mol, 1.95 eq.) water (48 mL) solution was added rapidly, controlling the rate of addition to ensure that the temperature did not exceed 4°C. A small amount of ether may be added at the appropriate time to minimize foaming during mixing. After the addition was complete, stirring was continued at less than 4°C for 1 hour. Subsequently, a 35% hydrochloric acid (24 mL) solution of pre-cooled stannous chloride (16.24 g, 0.072 mol, 2.4 eq.) was added and the mixture was stirred for 16 hours. After completion of the reaction, the brown solution was filtered and the resulting brown solid was washed with water to give a final light brown solid product (2.73 g, 51% yield). The NMR hydrogen spectral (MeOH-d4) data of the product were as follows: δH 7.25 (1H, td, J = 9.10 Hz and 2.14 Hz, ArH), 7.60 (1H, dd, J = 9.10 Hz and 4.28 Hz, ArH), 7.74 (1H, dd, J = 9.10 Hz and 2.10 Hz, ArH); LC-MS-EI showed the molecular ion peak m/z 183.1 (MH+, 100).
