反应 #62031

反应方程式

potassium acetate

isoamyl nitrite

ester

methyl 2-amino-3-methylbenzoate

acetic anhydride

chloroform

→

methyl 1H-indazole-7-carboxylate hydrochloride

收率 68.0%

反应条件

后处理

1. 1
   温度while maintaining the temperature below 40° C
2. 2
   workup.ADDITIONwas added
3. 3
   温度The reaction mixture was heated
4. 4
   温度at reflux for 24 h
5. 5
   洗涤The reaction mixture was washed with a saturated, aqueous solution of sodium bicarbonate
6. 6
   干燥dried over sodium sulfate
7. 7
   浓缩concentrated
8. 8
   workup.ADDITIONMethanol (100 mL) and 6 N hydrochloric acid (100 mL) were added to the residue
9. 9
   温度the mixture was maintained for 18 h at rt
10. 10
    其他The volatiles were removed under reduced pressure
11. 11
    其他the residue was triturated with ethyl acetate (100 mL)
12. 12
    其他The product was isolated by filteration
13. 13
    洗涤washed with ethyl acetate (20 mL)
14. 14
    其他dried

实验过程

To a solution of the ester (17.5 g, 106 mmol) in chloroform (300 mL) was added acetic anhydride (22.6 mL, 239 mmol, 2.3 eq) while maintaining the temperature below 40° C. The reaction mixture was maintained at room temperature for 1 h when potassium acetate (3.00 g, 30.6 mmol, 0.3 eq) and isoamyl nitrite (30.6 mL, 228 mmol, 2.2 eqiv) was added. The reaction mixture was heated at reflux for 24 h and was allowed to cool to room temperature. The reaction mixture was washed with a saturated, aqueous solution of sodium bicarbonate, dried over sodium sulfate, and concentrated. Methanol (100 mL) and 6 N hydrochloric acid (100 mL) were added to the residue and the mixture was maintained for 18 h at rt. The volatiles were removed under reduced pressure and the residue was triturated with ethyl acetate (100 mL). The product was isolated by filteration, washed with ethyl acetate (20 mL), and dried to provide 15.3 g (68%) of methyl 1H-indazole-7-carboxylate hydrochloride. 1H NMR (500 MHz, DMSO-d6) δ 13.3 (bs, 1H), 8.26 (d, 1H), 8.12 (d, 1H), 8.25 (dd, 1H), 7.27 (t, 1H), 3.97 (s, 3H); MS (APCI) m/z 177 (M++1).

来源