合成路线1

Bromination of 4-methoxy-2-methylbenzoic acid (I) with Br2 in the presence of Fe in CHCl3 yields 5-bromo-4-methoxy-2-methylbenzoicacid (II), which by chlorination with (COCl)2 in the presence of DMF in CH2Cl2 and subsequent Friedel-Crafts reaction with phenetole (III) by means of AlCl3 in CHCl3 affords the benzophenone derivative (IV). Reduction of the aryl ketone (IV) with BF3·Et2O in the presence of Et3SiH in acetonitrile/CHCl3 generates 1-bromo-5-(4-ethoxybenzyl)-2-methoxy-4-methylbenzene (V). Subsequent reaction of the aryl bromide (V) with Mg in the presence of BrCH2CH2Br in refluxing THF gives the corresponding Grignard reagent, which is then condensed with the thiolactone (VI) in THF to produce the 1-aryl-thioglucose derivative (VII), which is further reduced to the thioglucitol (VIII) using Et3SiH in the presence of BF3·Et2O in acetonitrile. Finally, thioglucitol (VIII) is debenzylated with H2 over Pd(OH)2/C in EtOAc/EtOH .
5-Bromo-4-methoxy-2-methylbenzoic acid (II) can alternatively be prepared by methylation of 4’-hydroxy-2’-methylacetophenone (IX) with methyl iodide by means of K2CO3 in acetone to give the 4’-methoxyacetophenone derivative (X), which is then treated with NaBr and oxone in acetone/water, providing a 4:1 mixture of 5’-bromo-4’-methoxy-2’-methylacetophenone (XI) and the 3’-bromo regioisomer (XII). Then, the mixture is treated with NaOCl and KOH at reflux and finally acidified with HCl .