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Recently, we published a synthesis of escitalopram (S-1) consisting of the resolution of didesmethylcitalopram (3) and subsequent methylation of S-didesmethylcitalopram (S-3) (Org. Process Res. Dev. 2007, 11, 289−292). Some of our observations regarding citalopram resolution and C-alkylation of a benzofuran analogue (2) to produce didesmethylcitalopram (3) were disputed by Dr. Dancer of H. Lundbeck (preceding article). A detailed response to his comments regarding stabilization of the 3-chloroproylamine free base by dilution with certain solvents, its storage and handling, optimized experimental conditions for C-alkylation to prepare didesmethylcitalopram, and a corrected process for citalopram resolution are included.

A simple and convergent approach to enantiomerically pure 5-[[2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one 1, a potent orally active antagonist of the human neurokinin-1 (NK-1) receptor, is described. The synthetic procedure starts from p-fluorobenzaldehyde to access the racemic morpholinone 2 via a modified Strecker synthesis and utilizes a diastereomeric salt resolution technique to accomplish the synthesis of 1 in enantiomerically pure form and good yield.

Application of a boric acid catalyzed process for the synthesis of the carboxamides, key reaction intermediates in the preparation of various active pharmaceutical ingredients (APIs), has been explored.

Enzyme‐catalyzed efficient synthesis of (1R)‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (R)‐(3), a key intermediate for aprepitant, via enantioselective transesterification of racemic 1‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (RS)‐3 using vinyl acetate as the acyl donor in the presence of Candida antarctica lipase‐B (CAL‐B) in an overall yield of 84% with >99% ee is described.

Research work presented here describes an approach to achieve the enantiopure escitalopram (1) via didesmethyl escitalopram (4), which is easily resolvable compared to citalopram (1a) through diastereomeric salt crystallization. The resolved intermediate (didesmethylcitalopram) was subsequently used for the preparation of the desired drug. This simple modification of the substrate makes a remarkable difference in the chemical resolution process. The first resolution of didesmethylcitalopram (±)-4 to furnish (+)-4, a novel key intermediate to assemble escitalopram (1) was achieved via diastereomeric salt resolution using (−)-di-p-toluoyltartaric acid (DPTTA). The resolution conditions were optimized; a key feature of this process is the addition of specific quantity of water at a specific temperature to the reaction mixture.

Telmisartan (1), a substituted dibenzimidazole derivative, is an antihypertensive drug, essentially used to control blood pressure. An improved, cost-effective, and impurity-free process for telmisartan (1) suitable for large-scale production is described here by addressing various process development issues. The overall yield obtained from this newly developed process is around 50% (over five steps) compared to the literature reported process (21%, over eight steps).

A new, economical, and efficient process has been developed for large‐scale synthesis of donepezil 1, an anti‐Alzheimer's drug. The process involves palladium‐catalyzed hydrogenation of (2E)‐5,6‐di...

An alternative and scalable synthesis of dexlansoprazole ((R)-(+)-1); the (R)-enantiomer of Lansoprazole with an enantiomeric excess of >99.8% is presented.

Solvent effects were studied in the stereoselective hydrogenation of methyl 3-oxo-4-aza-5-androstene-17-carboxylate (7) using re-activated Pd/C (type 39K) as a catalyst to furnish methyl 3-oxo-4-aza-5-α-androstene-17-carboxylate (2a), a common key intermediate for finasteride (1a) and dutasteride (1b), and reaction conditions were optimized to provide the required isomer with better selectivity.

An efficient and alternative synthesis of enantiomerically pure (3S)-4-benzyl-3-(4-fluorophenyl)morpholin-2-one (S)-(+)-2), a key intermediate in the synthesis aprepitant (1), is described. The key resolution of N-benzylglycinamide, (±)-9, is achieved via diastereomeric salt crystallization using (+)-di-p-toluoyltartaric acid (DPTTA) as the resolving agent to furnish (S)-(+)-9. Alkylation of (S)-(+)-9 with 2-bromoethanol followed by stereocontrolled cyclization of obtained (S)-(+)-10 afforded the desired enantiomer (S)-(+)-2 with good yields and enantiopurity (>98%). The reaction conditions were optimized to make the process robust in order to implement at the commercial scale.

Enzyme‐catalyzed efficient synthesis of (1R)‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (R)‐(3), a key intermediate for aprepitant, via enantioselective transesterification of racemic 1‐[3,5‐bis (trifluoromethyl) phenyl] ethanol (RS)‐3 using vinyl acetate as the acyl donor in the presence of Candida antarctica lipase‐B (CAL‐B) in an overall yield of 84% with >99% ee is described.

The development of a large-scale synthesis for (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine (S-(+)-1), a key intermediate of repaglinide (2), is described. The process conditions for S-(+)-1 involving nucleophilic substitution, Grignard reaction, reduction and resolution were optimized and telescoped. The racemization of the undesired enantiomer R-(?)-1 offers a distinctive advantage in terms of cost and overall yield over the existing process. This communication also describes the control of a DcU byproduct obtained during the condensation of S-(+)-1 with phenyl acetic acid derivative 3 in the synthesis of 2.

A new, economical, and efficient process has been developed for large‐scale synthesis of donepezil 1, an anti‐Alzheimer's drug. The process involves palladium‐catalyzed hydrogenation of (2E)‐5,6‐di...