関与物質
| 役割 | 名称 | HCID | 仕込み量 |
|---|
| 反応物 | 1-(Benzyloxy)-3-bromobenzene | HCID 2756638 | — |
| 反応物 | 2-Methyl-6-(trifluoromethoxy)-1H-indole | HCID 12180669 | — |
| 試薬 | Sodium t-butoxide | HCID 23676156 | — |
| 触媒 | 2-(Di-tert-butylphosphino)biphenyl | HCID 2734215 | — |
| 触媒 | Bis(dibenzylideneacetone)palladium | HCID 9811564 | — |
| 溶媒 | Toluene | HCID 1140 | — |
| 生成物 | 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole | HCID 59216720 | 62.48% |
反応手順
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.
情報源と証拠
| 出典データセット | 750 AstraZeneca ELN dataset |
|---|
| ORD ID | ord-f89f3a46444e42c0973a5acc34e50e60 |
|---|
| 出典メモ | 750 AstraZeneca ELN dataset |
|---|
