Lithium Hydroxide → 4-Chloro-1H-indazole

Temperature

0 °C

To a 250 ml flask with stirbar was added 2-methyl-3-chloroaniline (8.4 ml, 9.95 g, 70.6 mmol), potassium acetate (8.3 g, 84.7 mmol) and chloroform (120 ml). This mixture was cooled to 0° C. with stirring. To the cooled mixture was added acetic anhydride (20.0 ml, 212 mmol) drop wise over 2 minutes. The reaction mixture was warmed to 25° C. and stirred for 1 hour. At this point, the reaction was heated to 60° C. Isoamyl nitrite (18.9 ml, 141 mmol) was added and the reaction was stirred overnight at 60° C. Once complete, water (75 ml) and THF (150 ml) were added and the reaction was cooled to 0° C. LiOH (20.7 g, 494 mmol) was added and the reaction was stirred at 0° C. for 3 hours. Water (200 ml) was added and the product was extracted with EtOAc (300 ml, 100 ml). The organic layers were combined, dried with MgSO4 and concentrated in vacuo to yield 11.07 g 4-chloro-1H-indazole (100%) as an orange solid. 1H NMR (400 MHz, CDCl3) δ 8.18 (d, J=1 Hz, 114), 7.33 (d, J=8 Hz 1H), 7.31 (t, J=7 Hz, 1H), 7.17 (dd, J=7 Hz, 1 Hz 1H). LCMS (ESI pos) m/e 153 (M+1).

1. temperatureThe reaction mixture was warmed to 25° C.
2. stirringstirred for 1 hour
3. temperatureAt this point, the reaction was heated to 60° C
4. stirringthe reaction was stirred overnight at 60° C
5. temperaturethe reaction was cooled to 0° C
6. stirringthe reaction was stirred at 0° C. for 3 hours
7. extractionthe product was extracted with EtOAc (300 ml, 100 ml)
8. dry with materialdried with MgSO4
9. concentrationconcentrated in vacuo

ORD record

ord-54e5a4d274e24a02865844cb45e5c84e

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158626B2