Methyl iodide → 3-Iodo-1-methyl-1H-indazole

Temperature

0 °C

In a 50 ml round-bottomed flask, 3-iodo-1H-indazole (1.0 g, 3.9 mmol) was dissolved in THF (12 ml) and the solution was cooled to 0° C. Potassium tert-butoxide (612 mg, 5.45 mmol) was added and the reaction mixture was stirred at 0° C. for 1.25 h. Methyl iodide (0.29 ml, 4.64 mmol) was added dropwise then the ice bath was removed and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over silica gel with EtOAc/Hexanes (gradient 0-10% EtOAc) to afford 863 mg (86%) of 3-iodo-1-methyl-1H-indazole as a yellow oil. 1H NMR (CDCl3, 300 MHz): δ (ppm) 7.42-7.53 (m, 2H), 7.33-7.40 (m, 1H), 7.22 (ddd, J=8.0, 6.9, 0.9 Hz, 1H), 4.11 (s, 3H).

1. customthe ice bath was removed
2. stirringthe reaction mixture was stirred at room temperature for 2 h
3. customThe reaction mixture was quenched with water
4. extractionextracted with EtOAc (2×)
5. washThe combined organic layers were washed with water and brine
6. dry with materialthen dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by chromatography over silica gel with EtOAc/Hexanes (gradient 0-10% EtOAc)

ORD record

ord-1cb78558e6f24973a84b10882cefc2a6

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2