反应详情

温度

100 °C

A 100 mL round-bottomed flask was charged with (S)-2-methyl-4-(2-thiophenylsulfonyl)piperazine hydrochloride (10.0 g, 35.4 mmol), 2-(4-bromophenyl)-1,1,1-trifluoro-2-propanol (16.7 g, 61.9 mmol, Example 27, step 1), sodium tert-butoxide (13.6 g, 141 mmol) and 20 mL of toluene. To this was added dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (RuPhos) (1.98 g, 4.24 mmol, Strem Chemical Inc, Newburyport, Mass.), tris(dibenzylideneacetone)dipalladium (0) (1.94 g, 0.265 mmol, Strem Chemical Inc, Newburyport, Mass.). The mixture was heated at 100° C. for 12 h. After that time, the reaction was diluted with water (100 mL) and extracted with EtOAc (2×150 mL). The combined extracts were dried (MgSO4) and concentrated and purified by column chromatography (330 g of silica, 0 to 50% EtOAc in hexanes) to give 1,1,1-trifluoro-2-(4-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (13.20 g) as a mixture of two isomers.

1. extractionextracted with EtOAc (2×150 mL)
2. dry with materialThe combined extracts were dried (MgSO4)
3. concentrationconcentrated
4. custompurified by column chromatography (330 g of silica, 0 to 50% EtOAc in hexanes)