With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.17261-28-8,2-(Diphenylphosphino)benzoic acid,as a common compound, the synthetic route is as follows.
17261-28-8, Thus, crotonaldehyde was treated with HCN in the presence of an (R)-oxynitrilase readily obtained from grinding and scouring of bitter almonds,18 which gave the (R)-cyanohydrin with high levels of enantioselectivity (>96percent ee).19 Subjecting to the conditions of a Pinner reaction furnished the ethyl ester 20 (Scheme 6).20 The reduction with lithium aluminum hydride led to diol 21 and subsequent silylation furnished the silylether 22 on a multigram scale.21 Applying the standard Steglich esterification protocol22 with ortho-diphenylphosphanylbenzoic acid (o-DPPBA)23 provided o-DPPB-ester (R)-(+)-6 quantitatively. Crystallization of this product improved the enantiopurity to greater than 99percent ee. In order to obtain the requested (S)-enantiomer of 6 one could apply a corresponding (S)-oxynitrilase. However, such enzymes are far more difficult to access.24 Hence, we looked at a Mitsunobu inversion protocol, which ideally would use o-DPPBA itself as the nucleophile.25 Since o-DPPBA is both a carboxylic acid and a phosphine we expected this to be a non trivial reaction because the reagent triphenylphosphine as well as o-DPPBA may react with the azodicarboxylate electrophile. Interestingly, we observed a clean Mitsunobu reaction of the allylic alcohol 22 with o-DPPBA to furnish the corresponding (S)-(-)-enantiomer of o-DPPB-ester 6 in good yield (81percent). After recrystallization (S)-(-)-6 was obtained in >99percent enantiopurity.
The synthetic route of 17261-28-8 has been constantly updated, and we look forward to future research findings.
Reference£º
Patent; Albert-Ludwigs-Universitat Freiburg; US2011/282075; (2011); A1;,
Phosphine ligand
Chiral phosphine ligands in asymmetric synthesis. Molecular structure and absolute configuration of (1,5-cyclooctadiene)-(2S,3S)-2,3-bis(diphenylphosphino)butanerhodium(I) perchlorate tetrahydrofuran solvate