Acetonitrile → 2-(4-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol

Participants

Reaction Conditions

Reaction Steps

A 10 mL vial was charged with ((2R)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl methanesulfonate (0.207 g, 0.391 mmol, Intermediate B), 6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (endo) (0.100 g, 0.391 mmol, J. Org. Chem. 2010, 75, 1643), potassium carbonate (0.162 g, 1.173 mmol), and 3 mL of MeCN. The tube was sealed and heated in a microwave reactor (Emrys Optimizer Automated Microwave Synthesizer, Uppsala, Sweden) at 150° C. for 1 h. The mixture was diluted with EtOAc, filtered and the filtrate was concentrated and purified via column chromatography on silica gel (0 to 50% EA/Hex) to 2-(4-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol as a mixture of four endo isomers (0.130 g).

Provenance & Evidence