< >建议换条路线 < >我做过5-羟基-1-氢-吲唑，先将原料完全乙酰化，再用亚硝酸异戊酯高温合环，然后盐酸甲醇溶液脱去两个乙酰基，就得产品。收率70%以上。 < >1h-5-indazolol (12). to a mixture of 4-amino-3-cresol 11 (12.3 g, 100 mmol) and potassium acetate (24.4 g, 244 mmol) in chcl3 (200 ml), acetic anhydride (47.1 ml, 450 mmol) was added dropwise at 0℃ . the resulting mixture was stirred at rt for 30 min, heated
to 80℃ , followed by the dropwise addition of isoamylnitrite (12.7 g, 110 mmol) at 80℃ . the reaction mixture was stirred at 80℃ for 18 h and quenched by the addition of saturated nahco3 aq. the reaction mixture was extracted with chcl3. the combined organic layer was dried over anhydrous na2so4 and filtered.
the filtrate was then concentrated. the residual oil was subjected to flash chromatography on silica gel eluting with chcl3–meoh to give n,o-diacetyl-5-indazolol, which was then treated with hcl–meoh (200 ml) at 80℃ for 5 h and evaporated to remove hcl–meoh. the resulting mixture was basified with saturated nahco3 aq. the mixture was extracted with etoac. the combined organic layer was dried over anhydrous na2so4 and filtered. the filtrate was then concentrated. the precipitate was washed with chcl3 to give the title compound as a brown solid (7.99 g,60 mmol, 60% yield). 1h nmr (cdcl3, 400 mhz) d 6.95 (d, j = 8.8 hz, 1h), 7.03 (s, 1h), 7.31 (d,j = 8.8 hz, 1h), 7.89 (s, 1h). < >文献:m. iwakubo et al. / bioorg. med. chem. 15 (2007) 350–364 [此贴子已经被作者于2008-4-12 21:34:05编辑过]
