Hydrochloric Acid → HCID 68708210, compound

Participants

Reaction Steps

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%).

Provenance & Evidence