2-Methyl-4-methoxyaniline → 5-Methoxy-1H-indazole

Temperature

0 °C

A solution of 4-methoxy-2-methylaniline (2 ml) in dichloromethane (10 ml) was treated with triethylamine (3.27 ml). The mixture was cooled to 0° C. then treated with acetic anhydride (2.38 ml), then stirred at ambient temperature for 1 hour, then cooled to 0° C. when a pink solid precipitated. This solid was filtered, then washed with cold dichloromethane and then dissolved in acetic acid (55 ml) and concentrated hydrochloric acid (20 ml). This solution was cooled to −5° C., then treated with a solution of sodium nitrite (2.68 g) in water (20 ml), then stirred at that temperature for 1 hour and then treated with water (100 ml). This mixture was stirred vigorously at 0° C. for 10 minutes after which a yellow solid precipitated. This solid was filtered, then washed with water and then dissolved in toluene (13 ml). This solution was heated to 80° C. for 1.5 hours, then cooled and then washed with aqueous 1N sodium carbonate solution. The organic phase was extracted three times with aqueous 2N hydrochloric acid and the acid extracts chilled and then made alkaline by addition of aqueous 5N sodium hydroxide solution. The aqueous layers were extracted three times with ethyl acetate and the combined organic layers were dried over magnesium sulfate and then evaporated to yield 5-methoxy-1H-indazole (0.410 g) as a yellow solid. LC-MS (METHOD B): RT=1.32 minutes; 149 (M+H)+.

1. temperaturecooled to 0° C. when a pink solid
2. customprecipitated
3. filtrationThis solid was filtered
4. washwashed with cold dichloromethane
5. dissolutiondissolved in acetic acid (55 ml)
6. temperatureThis solution was cooled to −5° C.
7. additiontreated with a solution of sodium nitrite (2.68 g) in water (20 ml)
8. stirringstirred at that temperature for 1 hour
9. additiontreated with water (100 ml)
10. stirringThis mixture was stirred vigorously at 0° C. for 10 minutes after which a yellow solid
11. customprecipitated
12. filtrationThis solid was filtered
13. washwashed with water
14. dissolutiondissolved in toluene (13 ml)
15. temperatureThis solution was heated to 80° C. for 1.5 hours
16. temperaturecooled
17. washwashed with aqueous 1N sodium carbonate solution
18. extractionThe organic phase was extracted three times with aqueous 2N hydrochloric acid
19. temperaturethe acid extracts chilled
20. additionby addition of aqueous 5N sodium hydroxide solution
21. extractionThe aqueous layers were extracted three times with ethyl acetate
22. dry with materialthe combined organic layers were dried over magnesium sulfate
23. customevaporated

ORD record

ord-b8a758728546433c98bb20cd0ff3b91b

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288425B2