title: Additive free preparative chiral SFC separations of 2,2-dimethyl-3-aryl-propanoic acids.
abstract: A series of racemic 2,2-dimethyl-3-aryl-propanoic acids were resolved by chiral supercritical fluid chromatography (SFC) without the use of an acidic additive, trifluoroacetic acid (TFA). The use of additive-free protic methanol as co-solvent in CO2was expanded to successfully resolve other series of carboxylic acid containing racemates. Large-scale SFC of racemic acid 4, 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid, in methanol without TFA as additive on both Chiralpak AD-H and Chiralcel OJ-H will be discussed, along with impact on throughput and solvent consumption. Investigation of co-solvent effect on peak sharpening of acid racemate 20, 2-(2-chloro-9-fluoro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid, without TFA further indicated that methanol in CO2provided improved peak shape compared with isopropanol (IPA) and acetonitrile. Finally, we discuss the resolution of basic aromatic chiral amines without the addition of basic additives such as diethylamine (DEA) and application of this protocol for the large-scale SFC separation of weakly basic indazole-containing racemate 14, methyl 3-(1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoate, in methanol without DEA.
authors: Bristol-Myers Squibb Co., Research and Development, Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA. Electronic address: dauh-rurng.wu@bms.com.
authors: Dauh-Rurng
authors: DR
authors: Wu
authors: Bristol-Myers Squibb Co., Research and Development, Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors: Shiuhang Henry
authors: SH
authors: Yip
authors: Bristol-Myers Squibb Co., Research and Development, Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors: Peng
authors: P
authors: Li
authors: Bristol-Myers Squibb Co., Research and Development, Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors: Dawn
authors: D
authors: Sun
authors: Bristol-Myers Squibb Co., Research and Development, Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors: James
authors: J
authors: Kempson
authors: Bristol-Myers Squibb Co., Research and Development, Route 206 & Province Line Rd, Princeton, NJ 08543-4000, USA.
authors: Arvind
authors: A
authors: Mathur
mesh_terms: D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D010421:Pentanoic Acids / Q000032:analysis* / Q000737:chemistry*
chemical_list: D010421:Pentanoic Acids; C005566:pivalic acid
keywords: Acid additive; Additive-free; Chiral acids; Chiral supercritical fluid chromatography; Large scale