合成路线1

4) The reaction of racemic omeprazole (VII) with formaldehyde in dichloromethane gives, after crystallization in acetonitrile, 1-(hydroxymethyl)-6-methoxy-2-(4-methoxy-3,5-dimethyl-2-pyridinylmethylsulfinyl)-1H-benzimidazole (VIII), which is treated with SOCl2 in dichloromethane to afford, after crystallization in acetonitrile, the corresponding chloromethyl derivative (IX). The condensation of (IX) with (R)-2-hydroxy-2-phenylacetic acid (X) by means of NaOH and tetrabutylammonium hydrogen sulfate in water gives the corresponding ester (XI) as a diastereomeric mixture, which is resolved by reverse phase chromatography. Finally, the suitable isomer is hydrolyzed to esomeprazole by treatment with NaOH in methanol. (Scheme 27259802a) Esomeprazole magnesium can be obtained by three different ways: i) by reaction of esomeprazole with magnesium sulfate heptahydrate in aqueous ammonia; ii) by reaction of esomeprazole with magnesium methoxide in methanol or iii) by reaction of esomeprazole sodium, obtained by treatment of esomeprazole with NaOH in 2-butanone, with hydrated magnesium chloride in water. (Schemes 27259801a and 27259802a)