2-Chloro-6-methylaniline → 7-chloro-1H-indazole

Temperature

7.5 °C

A solution of 2-chloro-6-methyl-phenylamine (500 mg, 3.53 mmol) in H2SO4 (1.37 mL) was diluted by adding over 15 min. 2 mL of water in order to maintain a temperature below 90° C. Then the reaction mixture was cooled to 5-10° C. and a solution of sodium nitrite (246 mg, 3.57 mmol) in water (1 mL) was added over 2 hours. The resulting diazonium solution was then added to a solution of sodium acetate (5.21 g, 63.6 mmol) in water (20 mL) at a temperature maintained between 65 to 75° C. The resulting precipitate was filtered and treated with a solution of NaOH (6.00 g) in water (100 mL) at 95-100° C. The aqueous phase was separated while hot from the small amount of black tarry by-products, cooled to 50-60° C. and acidified with HCl (37%, 12.5 mL). The reaction mixture was cooled down to room temperature, the resulting precipitate was filtered, was washed thrice with cold water and was dried under vacuum to yield 7-chloro-1H-indazole (220 mg, 1.44 mmol, 41%) as a white solid.

1. additionby adding over 15 min
2. temperaturemaintained between 65 to 75° C
3. filtrationThe resulting precipitate was filtered
4. additiontreated with a solution of NaOH (6.00 g) in water (100 mL) at 95-100° C
5. customThe aqueous phase was separated while hot from the small amount of black tarry by-products
6. temperaturecooled to 50-60° C.
7. temperatureThe reaction mixture was cooled down to room temperature
8. filtrationthe resulting precipitate was filtered
9. washwas washed thrice with cold water
10. customwas dried under vacuum

ORD record

ord-34f2c59ed24146c7971ea62ea2c5837c

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08674106B2