A novel process for the synthesis of tetrabenazine (1) and deutetrabenazine (2), two well-known drugs used for the treatment of chorea associated with Huntington’s disease, has been developed. All of the reaction parameters were optimized through a series of reactions and by using Design of Experiment techniques. The newly developed methods are industrially scalable and employ cheap, commercially available raw materials and hence are highly efficient. The added advantage is that the developed processes evade the use of genotoxic alkylating agents and therefore could be considered as safe and viable alternatives to the existing methods.

A convenient and practical synthesis of imidazol-1-yl-acetic acid hydrochloride was achieved via N-alkylation of imidazole using tert-butyl chloroacetate followed by a non-aqueous ester cleavage of the resulting imidazol-1-yl-acetic acid tert-butyl ester in the presence of titanium tetrachloride. The synthesized imidazol-1-yl-acetic acid hydrochloride was then utilized to prepare zoledronic acid.

We describe an efficient process for the preparation of isotretinoin (13-cis isomer of vitamin A acid) in a single step starting from β-ionylidene acetaldehyde (5). The process conditions are convenient to operate on a commercial scale and afford isotretinoin of excellent quality; levels of related isomeric impurities such as tretinoin (all trans retinoic acid) and 9,13-di-cis-retinoic acid are extremely low. Thus, condensation of dienolate of methyl 3,3-dimethylacrylate with β-ionylidene acetaldehyde (5) followed by aqueous acidic workup afforded isotretinoin in >95% purity. The condensation reaction proceeds via in situ formation of lactone (8); furthermore, the reaction conditions have been optimized to exploit in situ generated methoxide anion for lactone ring opening to afford the desired product. Distinct advantages of this process are that it does not require isolation of intermediate lactone and utilizes in situ generated methoxide for lactone ring opening, thus obviating the need for an additional step and base. We also describe an optimized process for the preparation of β-ionylidene acetaldehyde (5), a key intermediate for isotretinoin.

A simple and rapid Supercritical Fluid Chromatography (SFC) Method has been developed to isolate and characterize the S-Isomer of Montelukast by using normal phase Amylose based AS-H with 250 mm × 30 mm, 5 microns column using a mobile phase system containing super critical fluid carbon dioxide (CO 2 ) and the percentage of 2-Propanol as a mobile phase (85:15) and detection at 230 nm. The isolated S-Isomer was characterized by using FT-IR, ESI-MS, HPLC and 1H NMR. The purity of isolated S-Isomer is about 98%.

This report describes an efficient and commercially viable synthesis of 3-ethoxy-4-ethoxy-carbonyl-phenylacetic acid (1), a key intermediate for the preparation of repaglinide, an oral hypoglycemic agent, from 2-hydroxy-4-methylbenzoic acid in two steps. Thus, 2-hydroxy-4-methylbenzoic acid was first alkylated with ethyl bromide in a polar aprotic solvent and in the presence of an inorganic base to afford ethyl 2-ethoxy-4-methylbenzoate; deprotonation with lithium diisopropylamide (LDA) and quenching the resulting carbanion with carbon dioxide provided the desired compound with improved yield and excellent purity. This procedure is significantly better than a previously published synthesis which involves five steps and requires use of expensive and hazardous reagents.