Sodium Bicarbonate → 4-(((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-(1-methylethyl)-2-piperazinone

Participants

Reaction Conditions

Reaction Steps

3-(1-methylethyl)-4-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-2-piperazinone (228 mg, 0.337 mmol) and iron filings (94 mg, 1.69 mmol, Sigma-Aldrich, St. Louis, Mo.) were combined in acetic acid (7.18 mL). The reaction mixture was stirred at 50° C. for 1.5 h. The mixture was allowed to cool to room temperature and saturated aqueous NaHCO3 was slowly added. After partitioning with EtOAc, the aqueous phase was extracted with EtOAc (×3). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to give a light brown oil. The crude product was purified by silica gel chromatography (25 to 75% EtOAc in hexanes gradient) to give a mixture of diastereomers which were separated via preparative SFC (Chrialpak® ASH (21×250 mm, 5 μm)), eluting with liquid CO2 in 30% methanol with 20 mM NH3, at a flow rate of 65 mL/min (40° C.), to give two products in >95% diastereomeric excess and >98% purity:

Provenance & Evidence