1-(Benzyloxy)-3-bromobenzene → 2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole

참여 물질

역할	이름	HCID	투입량
반응물	1-(Benzyloxy)-3-bromobenzene	HCID 2756638	—
반응물	2-Methyl-6-(trifluoromethoxy)-1H-indole	HCID 12180669	—
시약	Sodium t-butoxide	HCID 23676156	—
촉매	2-(Di-tert-butylphosphino)biphenyl	HCID 2734215	—
촉매	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
용매	Toluene	HCID 1140	—
생성물	2-Methyl-1-(3-phenylmethoxyphenyl)-6-(trifluoromethoxy)indole	HCID 59216720	62.48%

반응 조건

온도	80 °C

반응 단계

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.

출처 및 근거

출처 데이터셋	750 AstraZeneca ELN dataset
ORD ID	ord-f89f3a46444e42c0973a5acc34e50e60
출처 메모	750 AstraZeneca ELN dataset