反应详情

NaH (5 eq, 60% dispersion in mineral oil) was added to a degassed solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in published International patent application WO2006/046030) in DMF (0.2 M) and the solution was allowed to stir for 20 min at RT. The mixture was then placed in an oil bath preheated at 70° C., a degassed solution of 5,5-bis(bromomethyl)-2,2-dimethyl-1,3-dioxane (1.5 eq) in dry DMF (0.4M) was added and the mixture was stirred for 1 h; additional electrophile (1.5 eq) was added and stirring was continued for 3 h at 70° C. The reaction was quenched with sat. aq. NH4Cl, acidified with 1N HCl and extracted with Et2O; the organic layer was washed with H2O and brine, dried over Na2SO4 and the solvent was removed in vacuo. The crude was purified by FC (PE/EtOAc) to afford the title compound (50%) and recovered starting material (44%). (ES+) m/z 490 (M+H)+.

1. customThe mixture was then placed in an oil bath
2. custompreheated at 70° C.
3. stirringthe mixture was stirred for 1 h
4. additionadditional electrophile (1.5 eq) was added
5. stirringstirring
6. waitwas continued for 3 h at 70° C
7. customThe reaction was quenched with sat. aq. NH4Cl
8. extractionextracted with Et2O
9. washthe organic layer was washed with H2O and brine
10. dry with materialdried over Na2SO4
11. customthe solvent was removed in vacuo
12. customThe crude was purified by FC (PE/EtOAc)