Page 234 - Chiral Separation Techniques
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212     8 Nonchromatographic Solid-Phase Purification of Enantiomers


                                                   +
                                       NapCH(Me)NH3 ClO –
                                                      4
                  16.0
                Concentration [mg/ml]  10.0  R                       S
                  14.0
                  12.0
                   8.0
                   6.0
                   4.0
                   2.0
                   0.0
                      60     75     85     95    105    115    125    135    145
                                            Volume of eluent [ml]
                                                 –
               Fig. 8-4. Separation of R and S NaPEtNH  +  ClO by a supported chiral macrocyclic ligand.
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               8.5.2 Automated Test Demonstration

               In our laboratories at IBC, we have developed, synthesized and tested several chiral
               stationary phases to verify the enantiomeric discrimination capability. A few of these
               phases have been made in sufficient quantity to allow for multiple stage system test-
               ing and obtaining of the associated parameters for engineering design of process-
               scale systems. In this section, we discuss the results and implications for commer-
               cial-scale system operation. In order to assess the potential of MRT for meeting the
               industry separations needs, laboratory demonstrations are being performed at IBC.
               An automated, three-stage separations system was built for demonstration of actual
               full recovery and purification of both enantiomers from a 50/50 feed stream. One,
               two or three stages can be used for the separation so that percent purity values in the
               high 90s can be obtained with α values 6 4. The system operates in a manner sim-
               ilar to the process description in Section 8.3 and Fig. 8-3. The system includes up
               to three lead/trail columns per stage to allow for three columns in series to be oper-
               ative or elution of one column in a stage while the other two columns are in load
               operation. Stage recycles, feedstock vessels, and other accessories are present to
               allow for full engineering demonstration and testing the economics, chemicals and
               equipment advantages of a nonchromatographic system. The compound chosen for
               initial evaluation was valine, (CH ) CHCH(NH )COOH. This amino acid was cho-
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               sen as representative of a relatively difficult separations case for racemic amino
               acids. In addition to α-amino acids, the technology developed can be, or is expected
               to be, applied to β-substituted-β-amino acids, chiral alcohols, and diols.
                 Enantiomer separation factors (α values) for valine and phenylalanine as well as
               their esters of 5–10 for phenylalanine and 4–10 for valine have been shown at the
               0.1–1 g ChiraLig TM  scale. These α values vary as a function of solvent and other
               loading matrix factors (pH, salts, etc.). However, all of these cases show α values
               high enough to obtain reasonable enantiometric purity in less than or equal to three
               stages. The system with α value of ≈ 6 for the valine methyl ester enantiomers has
               the ability to load the valine onto the resin in H O containing LiClO and also to
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