Cesium carbonate → HCID 76462375, compound

Participants

Reaction Conditions

Reaction Steps

2-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (102 mg, 0.18 mmol, Example 69), tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-yn-2-yloxy)silane (86 mg, 0.28 mmol, Combi-Blocks, San Diego, Calif.), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride, dichloromethane complex (15 mg, 0.02 mmol, Sigma-Aldrich, St. Louis, Mo.), and cesium carbonate (180 mg, 0.55 mmol) were combined in DME (1.2 mL) and water (0.1 mL). The reaction mixture was purged with nitrogen for several minutes, and then stirred and heated in an Emrys Optimizer microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 100° C. for 15 min and at 120° C. for 30 min. The reaction mixture was filtered through a pad of Celite® (diatomaceous earth) eluting with CH2Cl2 and the filtrate was concentrated in vacuo. The residue was suspended in 1N HCl (5 mL) and stirred at room temperature for 30 min. The mixture was partitioned between CH2Cl2 (5 mL) and saturated aqueous sodium bicarbonate (5 mL). The layers were separated, the organic material was dried (Na2SO4), filtered, and concentrated. The crude material was subjected to reverse-phase preparative HPLC using a Phenomenex Gemini C18 column (150×30 mm, 10 μm) eluting with 0.1% TFA in CH3CN/H2O (30% to 100% over 10 min) to provide 4-(2-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-3-butyn-2-ol (23 mg) as an off-white solid and a mixture of two enantiomers.

Provenance & Evidence