反应详情

A 0.1M solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as in WO2006/046030; Example 9, Step 1) in dry DMF was treated with solid K2CO3 (1.5 eq.) followed by neat benzyl bromide (1.0 eq.) via syringe. The resulting suspension was stirred overnight. 1N HCl was added and the mixture extracted into EtOAc. The organic layers were washed with water and brine, then dried over Na2SO4 and evaporated. The residue was triturated with small portions of pentane affording after drying methyl 2-[2-(benzyloxy)phenyl]-3-cyclohexyl-1H-indole-6-carboxylate as an off-white solid (93%). 60% NaH (2 eq.) was added to a 0.2M solution of this material (1.6 eq.) in dry DMF, after stirring for 20 min a 0.2M solution of [(7aS)-3-oxodihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7a(5H)-yl]methyl 4-nitrobenzenesulfonate (1 eq.) in dry DMF was added and stirring was continued at 65° C. for 4 h. After quenching with sat NH4Cl the mixture was extracted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated; flash chromatography (PE:EtOAc 2:1) afforded the title compound (48%).

1. extractionthe mixture extracted into EtOAc
2. washThe organic layers were washed with water and brine
3. dry with materialdried over Na2SO4
4. customevaporated
5. customThe residue was triturated with small portions of pentane affording
6. dry with materialafter drying methyl 2-[2-(benzyloxy)phenyl]-3-cyclohexyl-1H-indole-6-carboxylate as an off-white solid (93%)
7. additionwas added
8. stirringstirring
9. waitwas continued at 65° C. for 4 h
10. customAfter quenching with sat NH4Cl the mixture
11. extractionwas extracted with EtOAc
12. washwashed with water and brine
13. dry with materialdried over Na2SO4
14. concentrationconcentrated