反应详情

To a suspension of 3-bromo-7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole (D59) (100 mg), tris(1,1-dimethylethyl)phosphane (13 mg), Pd2(dba)3 (41 mg) and Cs2CO3 (30 mg) in THF (5 mL) stirred under nitrogen at room temperature was added a solution of bromo[(2S)-2-methyl-3-(methyloxy)-3-oxopropyl]zinc (1.0 M in THF, 2 mL) in one portion. The reaction mixture was stirred at 60° C. for 1.5 h. The mixture was cooled to room temperature and filtered. The filtrate was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was washed with water, aqueous HCl (2 M) and brine, dried over sodium sulphate and evaporated to afford methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate (D60) (120 mg). MS (ES): C25H26ClN3O4 requires 467; found 468.2 (M+H+).

1. stirringThe reaction mixture was stirred at 60° C. for 1.5 h
2. temperatureThe mixture was cooled to room temperature
3. filtrationfiltered
4. customThe filtrate was partitioned between ethyl acetate (50 mL) and water (50 mL)
5. washThe organic phase was washed with water, aqueous HCl (2 M) and brine
6. dry with materialdried over sodium sulphate
7. customevaporated