2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → HCID 66582315, compound

Participants

Reaction Conditions

Reaction Steps

A 20 ml, vial was charged with 4-(2-thiophenylsulfonyl)piperazine hydrochloride (70 mg, 0.260 mmol), sodium tert-butoxide (45.7 mg, 0.476 mmol), tris(dibenzylideneacetone)dipalladium (0) (1.1 mg, 1.13 μmol, Strem Chemical Inc, Newburyport, Mass.), dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (1.6 mg, 3.40 μmol, Strem Chemical Inc, Newburyport, Mass.) and 2-(4-bromophenyl)-1,1,1-trifluoro-2-propanol (60.9 mg, 0.226 mmol, Example 27, step 1) in toluene (906 μL) was heated to 100° C. for 20 h. The reaction was then cooled to ambient temperature and additional tris(dibenzylideneacetone)dipalladium (0) (1.1 mg, 1.13 μmol, Strem Chemical Inc, Newburyport, Mass.) and dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (1.6 mg, 3.40 μmol, Strem Chemical Inc, Newburyport, Mass.) were added. The reaction was then heated to 100° C. for an additional 20 h. The reaction was cooled to ambient temperature and diluted with MeOH (2 mL). The reaction was loaded onto a 1 g AccuBOND II SCX cartridge, which was washed with MeOH (5 mL) and eluted with 2 N ammonia in MeOH (5 mL) to give the crude reaction mixture. The crude material was absorbed onto a plug of silica gel and purified by column chromatography (10 g of silica gel, 5%-45% EtOAc in hexanes) to provide 1,1,1-trifluoro-2-(4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol as a mixture of two enantiomers.

Provenance & Evidence