合成路线1

Selective mono-protection of 2,2-dibutyl-1,3-propanediol (X) using one equivalent of TBDMSCl and NaH in THF yields the TBDMS ether (XI), which is then oxidized by means of NaIO4 in the presence of a catalytic amount of RuCl3 in CCl4/acetonitrile/H2O, followed by desilylation with TBAF in THF to give the hydroxy acid (XII). Bromination of alcohol (XII) with concentrated HBr at reflux provides the bromo acid (XIII), which by condensation with 2-amino-5-methoxythiophenol (XIV) [prepared by hydrolysis of 2-amino-6-methoxybenzothiazole (XV) with KOH at reflux] by means of Et3N in DMF and subsequent cyclization using p-TsOH in refluxing tetradecane produces the 1,5-benzothiazepin-4-one derivative (XVI). Bromination of compound (XVI) with NBS in CH2Cl2 results in the 7-bromobenzothiazepinone (XVII), which is arylated with bromobenzene (XVIII) in the presence of CuBr and K2CO3 at reflux to afford the 5-phenylbenzothiazepinone derivative (XIX). Reduction of lactam (XIX) using AlH3 (generated in situ from LiAlH4 and H2SO4) in Et2O/THF followed by oxidation of the thioether moiety with NMMO and catalytic OsO4 in THF yields the sulfone (XX) , which is finally submitted to simultaneous bromide substitution and O-demethylation using MeSNa in the presence of NaBH4 in DMF at 120 °C .