Abstract

Rohidas Gilbile^1,2, Ram Bhavani² and Ritu Vyas¹

DOI : http://dx.doi.org/10.13005/ojc/330244

2-[[(2-pyridinyl) methyl] sulfinyl]-1H-benzimidazoles are the prominent motif’s that belong to the class of prazoles. These are used  in the treatment of gastroesophageal reflux disease (GERD) ulcers and other gastric acid related diseases. The present article describes the modified synthesis of 2-chloromethyl-4-methanesulfonyl-3-methyl pyridine (an intermediate utilized in the synthesis of Dexlansoprazole). The advantages of this modification involves (i) N-oxidation of 2,3-lutidine with catalytic quantity of RuCl₃ in presence of oxygen (ii) One pot synthesis of  2,3-dimethyl-4-(methylthio)pyridine-N-oxide using 30% NaSH, methyl iodide and tetra butyl ammonium hydroxide (iii) Oxidation of methythio pyridine–N-oxide with 30% H₂O₂ followed by N-deoxygenation with RuCl₃.H₂O  to produce 2,3-dimethyl-4-(methylsulfonyl)pyridine (iv) Chlorination of the penultimate step using trichloroisocyanuric acid to obtain the desired 2-chloromethyl-4-methanesulfonyl-3-methyl pyridine. Furthermore, green metrics assessment was calculated for the above modified scheme based on the parameters viz., atom economy (AE), reaction mass efficiency (RME) and E-factor. It was observed that, in case of step 4 (oxidation of thiomethyl pyridine-N-oxide), the E-factor value is very less 3.2 which is indicative of less waste generation, when compared to the various steps involved in the synthesis.

Atom economy; RME; E-Factor; Green metrics; Prazoles; Synthesis

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