Dhileepkumar Krishnamurthy

Asymmetric synthesis of cetirizine dihydrochloride

Abstract Practical route technology for the preparation of ( S )-cetirizine·2HCl via diastereoselective organometallic addition to N - tert -butanesulfinyl aldimines is disclosed.

Effective tuning of the arene and alkanesulfinamides for highly enantioselective synthesis of (S)-4-chlorophenylphenylmethylamine, a key intermediate for antihistamic (S)-cetirizine

High diastereoselectivity (>94%) has been achieved in the phenylMgBr addition process to chlorophenyl aldimine derived from the new and sterically hindered triisopropylbenzene sulfinamide (TIPBSA) in the synthesis of a key intermediate of (S)-Cetirizine. Surprisingly, under the same reaction conditions, toluenesulfinamide derived chlorophenyl aldimine provided only 10% ee.

First asymmetric synthesis of (R)-desmethylsibutramine ☆

Abstract A catalytic enantioselective addition of iBuLi to aldimine 3 derived from methyl amine and 1-(4-chlorophenyl) cyclobutanecarboxaldehyde is used as the key step in the asymmetric synthesis of (R)-desmethylsibutramine, a single enantiomer version of a pharmacologically active metabolite of anti-obesity drug sibutramine (Meridia®).

First practical synthesis of enantiomerically pure (R)- and (S)-desmethylsibutramine (DMS) and unambiguous determination of their absolute configuration by single-crystal X-ray analysis

A practical synthesis of enantiomerically pure (R)-desmethylsibutramine [(R)-DMS] and (S)-desmethylsibutramine [(S)-DMS] is outlined along with an improved synthesis of racemic desmethylsibutramine. This route was used for kilo-scale production of enantiomerically pure (R)- and (S)-DMS. Racemic desmethylsibutramine was resolved with either (R)- or (S)-mandelic acid, and the absolute stereochemistry of DMS was determined by single X-ray crystallography of its mandelate salt.