(Trifluoromethyl)trimethylsilane → HCID 67111469, compound

Participants

Reaction Steps

To a mixture of 3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)benzaldehyde (2.00 g, 5.34 mmol) and trimethyl(trifluoromethyl)silane (0.911 g, 6.41 mmol) in 20 mL THF under nitrogen at 0° C. was added TBAF 1.0 M in THF (0.534 mL, 0.534 mmol). The reaction mixture became immediately dark brown and homogeneous. The water bath was removed and the reaction mixture was allowed to stir for 3 h. 1N aq. HCl (20 mL) was added and the reaction mixture allowed to stir overnight. The reaction mixture was partitioned between water and DCM. The aqueous layer was extracted with DCM, and the combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was treated with DCM and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 0-20% EtOAc/hexane. The product-containing fractions were concentrated to afford racemic 2,2,2-trifluoro-1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanol as a pale yellow foam. The racemic mixture were separated by Multigram II SFC (Column: Chiralpak ADH (21×250 mm, 5 um); A=supercritical CO2; B=Isopropanol; 30% B, 65 mL/min total flow, 40° C., 100 bar outlet pressure) to give (R)-2,2,2-trifluoro-1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanol and (S)-2,2,2-trifluoro-1-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanol. MS (ESI) m/z: calculated: 444.1; Observed: 445.1 (M++1).

Provenance & Evidence