Chiracel OD-H columns

The checkers also prepared racemic 1-[N-benzyloxycarbonyl-(1 )-1-amino-2-hydroxyethyl]-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane using the identical procedure (50% over 2 steps from racemic Cbz-serine purchased from Aldrich Chemical Company, Inc.). The enantiomeric ratio of the crystalline (S)-3 enantiomer (Note 20) was > 99.5 0.5 as determined by comparison with racemic 3 by courtesy of Mr. Eric Hortense (GlaxoSmithKline, Stevenage). Chiral HPLC (25 cm Chiracel OD-H, Column No ODHOCE-IF029, mobile phase ethanol/heptane 1 4 v/v, UV detector at 215 nm, flow rate... 

The enantiomeric excess was determined by HPLC, using a Chiracel OD-H column (Chiral Technologies Europe, Illkirch, France), 250 x 4.6 mm, 5 jxm with guard cartridge, 0.5 mL min , 97 3 0.1 hexane iso-propanol tri-fluoroacetic acid, iR[(- -)-5] = 19 minutes, fR[(—)-/ ] = 17 minutes, tR[linear] =21 minutes. 

CH2CI2. The organic phase was washed with brine, dried (MgS04), and rotary evaporated. A purification by column chromatography (silica gel, 4% MeOH/CH2Cl2) afforded BMS-204352 in 96% yield. Ees were determined by chiral HPLC (Chiracel OD-H column, 10% 2-propanol/hexane, 1 mL.min l = 254nm, retention times (S)- BMS-204352 6.0 minutes, (R)-BMS-204352 7.8 minutes). 

The concentrations of benzaldehyde, the mixed product, and benzoin and the enantiomeric excesses (revalues) were determined by chiral-phase HPLC with a photodiode array detector. Chiral-phase HPLC was performed on a Chiracel OD-H (Daicel, Diisseldorf, Germany) using isohexane/isopropanol (90 10) as eluent, a flow rate of 0.5 mL min and a column oven at 40 °C. The retention time for benzaldehyde was 10.2 min, for the mixed product DMA-HPP 15.1 and 16.4 min, for the (S)-benzoin 20.3 min, and for the (R)-benzoin 28.5 min. 

Lacroix et al. compared an HPLC with a H NMR method for quantification of the R-enantiomer in S-timolol maleate, a -blocking substance (Figure 6-7) [17]. For satisfactory resolution, the HPLC required the expensive cellulose tris-3,5-dimethylphenylcarbamate column (Chiracel OD-H), a mobile phase of 0.2% dimethylamine and 4% isopropano in hexane and H NMR (400-MHz) R-TFAE as a CSA in CDCIj. The resonance of the tert-butyl group between 1.0 and 1.1 ppm was used to measure the ee. With both methods, 0.2- 4.0% of the R-enantiomer in S-timolol could be determined precisely. Additionally, both methods (HPLC and NMR) were found to be superior to specific rotation, which is used in the USP XXIII for determination of optical purity. This superiority of NMR and HPLC methods over optical rotation has often been reported [2],... 

The chiral separation of VX isomers was achieved using normal phase liquid chromatography with a Chiracel OD-H colrnnn. The separation of the enantiomers of VX was first described by Kientz et al. (1994). They used a thermo-ionic detector for the selective detection of phosphorus compoimds. Unfortunately, this technique was not robust enough. The same separation was also described by van der Schans et al. (2()03) using electrochemical detection. The mobile phase (hexaneiethanol 95 5) was mixed after the column procedure with 0.1 M lithimn perchlorate solution to ensure conductivity necessary for electrochemical detection. The system could be used to study the stereo-selective degradation of VX in in vitro samples such as liver homogenates and plasma. Although the electrochemical detection was... 

Epoxidation conditions Iminium salt (5 mol%), Oxone (2 equiv), Na2CO3 (4 equiv), MeCN H2O (1 1), 0 "C, 2 h. Enantiomeric excess determined by NMR with Eu(hfc)3 (0.1 mol equiv) as chiral shift reagent or by Chiral HPLC on a Chiracel OD column. 

Apart from the Chirasil-L-Val method, sarin enantiomers were also separated by a two-dimensional GC technique on chiral Cyclodex B material prior to NPD monitoring (Spruit et al., 2000,2001). Additional GC-based approaches allowed baseline separation of cyclosarin enantiomers on a GAMMA DEX column monitored by EI-MS (Reiter et al., 2007), separation of VX stereoisomers on hydrodex-p-TBDAc (p-cyclodextrin Reiter et al., 2008), and separation of tabun enantiomers on BetaDex 225 coupled to APCI-MS (Tenberken et al., 2010). VX enantiomers were also chromatographed on a Chiracel OD column by LC coupled to an electrochemical detector, yielding a lower limit of quantification of about lOng/mL blood (Van der Schans et al., 2003). Another LC method coupled with MS/MS detection for VX made use of CHIRALCEL OD-H and CHIRAL AGP columns (Reiter et al., 2008). 

---