반응 #62031

반응 방정식

potassium acetate

isoamyl nitrite

ester

methyl 2-amino-3-methylbenzoate

acetic anhydride

chloroform

→

methyl 1H-indazole-7-carboxylate hydrochloride

수율 68.0%

반응 조건

후처리

1. 1
   온도while maintaining the temperature below 40° C
2. 2
   workup.ADDITIONwas added
3. 3
   온도The reaction mixture was heated
4. 4
   온도at reflux for 24 h
5. 5
   세척The reaction mixture was washed with a saturated, aqueous solution of sodium bicarbonate
6. 6
   건조dried over sodium sulfate
7. 7
   농축concentrated
8. 8
   workup.ADDITIONMethanol (100 mL) and 6 N hydrochloric acid (100 mL) were added to the residue
9. 9
   온도the mixture was maintained for 18 h at rt
10. 10
    기타The volatiles were removed under reduced pressure
11. 11
    기타the residue was triturated with ethyl acetate (100 mL)
12. 12
    기타The product was isolated by filteration
13. 13
    세척washed with ethyl acetate (20 mL)
14. 14
    기타dried

실험 절차

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).

출처