Optical purification of profen drugs

Manimaran, T.; Stahly, G. Patrick

doi:10.1016/s0957-4166(00)80436-x

Cited by 29 publications

(16 citation statements)

References 2 publications

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“…Unfortunately, we were unable to crystallize an enantiomer-enriched ammonium carboxylate. Neither by variation of the solvent nor by pre-formation of the sodium salt possessing a different melting point phase diagram [13], could we favor crystallization of one enantiomeric species. We were not more successful with other chiral amines such as ephedrine, quinine, cinchonidine, or (À)-(1R,2R)-cyclohexane-1,2-diamine.…”

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confidence: 91%

“…Data 13 The soln. was allowed to reach 208, then heated under reflux (658), and stirred for 4 h. As the conversion was still low, more LiBHEt 3 (2 ml, 2.0 mmol) was added.…”

mentioning

confidence: 99%

“…182 ± 1858. 1 H-NMR: 1.12 (d, J 7, 3 H); 1.27 (s, 3 H); 1.30 (s, 3 H); 1.38 (s, 3 H); 1.48 (s, 3 H); 2.23 (2s, 6 H); 2.27 (m, 1 H); 2.82 (d, J 4, 1 H); 7.07 (2s, 2 H); COOH not visible 13. C-NMR: 180.1 (s); 141.0 (s); 140.8 (s); 134.0 (s); 133.9 (s); 127.9 (d); 127.0 (d); 54.0 (d); 38.8 (d); 37.0 (s); 35.8 (s); 34.7 (q); 33.8 (q); 27.9 (q); 26.6 (q); 19.5 (2q); 14.7 (q).…”

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confidence: 99%

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Syntheses of the Enantiomers ofVulcanolide®

Fehr

Chaptal-Gradoz

2002

HCA

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The synthesis of the enantiomers of Vulcanolide ¾ ((AE)-7) is described, the strongest musk odorant among hundreds of structurally related analogues, by resolution of an intermediate. To this end, we devised a new route which involves the temporary introduction of a modulable functional group in the vicinity of the stereogenic centers (Scheme 2). The resolution is based on the chromatographic separation of two diastereoisomeric camphanic acid esters. The strong and characteristic note of racemic Vulcanolide ¾ is almost entirely due to the (À)-enantiomer. This synthesis has allowed the preparation of new, structurally related musk odorants.

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confidence: 91%

“…Data 13 The soln. was allowed to reach 208, then heated under reflux (658), and stirred for 4 h. As the conversion was still low, more LiBHEt 3 (2 ml, 2.0 mmol) was added.…”

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confidence: 99%

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confidence: 99%

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Syntheses of the Enantiomers ofVulcanolide®

Fehr

Chaptal-Gradoz

2002

HCA

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“…Ibuprofen's (S) enantiomer is approximately 3 times more effective than its racemic form [38]. Optical resolution of ibuprofen has already been demonstrated with multiple technologies, such as crystallization from organic solution [39], making it a good basis of comparison when developing a resolution system. The resolution of ibuprofen was investigated and recommended with several different resolving agents, for example ephedrine [39], phenylethylamine [40] or lysine [41].…”

Section: Introductionmentioning

confidence: 99%

“…Optical resolution of ibuprofen has already been demonstrated with multiple technologies, such as crystallization from organic solution [39], making it a good basis of comparison when developing a resolution system. The resolution of ibuprofen was investigated and recommended with several different resolving agents, for example ephedrine [39], phenylethylamine [40] or lysine [41]. Resolution of ibuprofen with (S)-phenylglycinol was previously investigated by the in situ method, without any success [42].…”

Section: Introductionmentioning

confidence: 99%

Gas antisolvent fractionation based optical resolution of ibuprofen with enantiopure phenylglycinol

Lőrincz

Tóth

Kondor

et al. 2018

Journal of CO2 Utilization

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Fast Attrition‐Enhanced Deracemization of Naproxen by a Gradual In Situ Feed

et al. 2009

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In memory of Egbert Havinga, born 100 years ago Routes to create enantiomerically pure compounds starting from prochiral or racemic components are a principal issue in the discussion on the emergence of prebiotic chiral molecules. Such routes to single-handedness are also of paramount practical importance today, especially for economical highyielding processes to pharmaceutical compounds that often must be registered in enantiomerically pure form. [1] Louis Pasteur demonstrated that enantiomorphous crystals (a racemic conglomerate) of a tartrate salt could be separated manually.[2] Crystallization of a conglomerate is an attractive option to obtain enantiomerically pure materials, provided a better means of separation than manual crystal sorting is available. Resolution by crystallization is much more attractive if simultaneous racemization of the unwanted enantiomer occurs. This combination of crystallization and racemization in solution results in a so-called total spontaneous resolution, [3] for which enantiopure seeds are introduced into a clear supersaturated solution in which racemization takes place. These seeds grow further, resulting in an increasing amount of enantiopure solid material, until the solution is depleted of racemate. To reduce the nucleation rate of the undesired enantiomer, the supersaturation can be lowered by introducing many secondary nuclei of the desired enantiomer by stirring. [4,5] In principle, all chiral material that crystallizes can be converted into the desired enantiomer. The theoretical yield in enantiopure solid phase is thus 100 % and in practice only limited by solubility. To prevent the unwanted enantiomer from nucleating, however, the crystallization conditions, and in particular the temperature, need to be controlled well.The recent demonstration of a complete deracemization using crystallization with abrasive grinding under nearequilibrium conditions is a remarkably simple and much more reliable technique to reach an enantiomerically pure end state for these systems.[6] Recently we determined the rate-determining parameters for this deracemization process.[6d] In particular, we found that the deracemization time increases linearly with the amount of solids in the slurry. Furthermore, the time needed for the system to overcome the threshold of the autocatalytic process could be minimized by starting from an enantioenriched solid phase.[6c] Would it therefore be beneficial to start with a small amount of solids having a large enantiomeric excess (ee), and then gradually feed the slurry under isothermal conditions with racemic material? In this way, the solid phase can sustain a high ee, resulting in a high deracemization rate. Overall, this procedure should shorten the time required to reach an enantiopure solid phase.Although the gradual feeding can be realized mechanically, the target molecule can be alternatively synthesized in situ, making the practical execution very simple. To show the practical applicability, the non-steroidal anti-inflammatory drug (S)-naproxen i...

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Optical purification of profen drugs

Cited by 29 publications

References 2 publications

Syntheses of the Enantiomers ofVulcanolide®

Syntheses of the Enantiomers ofVulcanolide®

Gas antisolvent fractionation based optical resolution of ibuprofen with enantiopure phenylglycinol

Fast Attrition‐Enhanced Deracemization of Naproxen by a Gradual In Situ Feed

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