参与物
| 角色 | 名称 | HCID | 投料 |
|---|
| 反应物 | 3-苄氧基溴苯 | HCID 2756638 | — |
| 反应物 | 2-甲基-6-三氟甲氧基吲哚 | HCID 12180669 | — |
| 试剂 | 叔丁醇钠 | HCID 23676156 | — |
| 催化剂 | 2-(二叔丁基膦)联苯 | HCID 2734215 | — |
| 催化剂 | 三(二亚苄基丙酮)二钯 | HCID 9811564 | — |
| 溶剂 | 甲苯 | HCID 1140 | — |
| 产物 | 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole | HCID 59216720 | 62.48% |
反应步骤
EN04773-54, _Buchwald coupling, toluene and bromide_ The indole from 4773-41, 1-(benzyloxy)-3-bromobenzene,Pd2(dba)3 (5mol%), JohnPhos (10mol%) and KOtBu (1.4eq) were dissolved in toluene. The mixture was warmed at 80 °C for 40 hours.* The reaction was carefully monitored and analysis data from 2h, 4, 16 and 40 h are attached. According to LCMS there were ca 75% conversion to the product. The mixture was washed with water, concentrtaed and purified by silica column (Hep/EtOAc 6:1). The collected fractions contained product (6 g, 62.5% yield) but had some impurity (see TLC and NMR). Nevertheless Friedel crafts acylation was performed without further purifications. See e.g. 4773-56. ### *JohnPhos, pd2(dba)3 and sodium tertbutoxide had been dissolved in toluene and was portionwise added to the reaction mixture during the first 16h.
来源与证据
| 来源数据集 | 750 AstraZeneca ELN dataset |
|---|
| ORD ID | ord-f89f3a46444e42c0973a5acc34e50e60 |
|---|
| 来源说明 | 750 AstraZeneca ELN dataset |
|---|
