合成路线1

A synthesis of Sch-42427, the active (RR)-enantiomer of Sch-39304, has been published: The condensation of 1,3-difluorobenzene (I) with (S)-2-chloropropionyl chloride (II) by means of AlCl3 gives 2(S)-chloro-1-(2,4-difluorophenyl)-1-propanone (III), which is reduced with NaCNBH3 to the corresponding alcohol (IV). Epoxidation of (IV) with K2CO3 in methanol yields the chiral epoxide (V). The oxidative opening of (V) by means of BF3 in DMSO affords (R)-1-(2,4-difluorophenyl)-2-hydroxypropanone (VI), which is protected with dihydropyran (DHP) and p-toluenesulfonic acid to the tetrahydropyranyl ether (VIII). Alternatively, the treatment of (V) with trimethylsilyl bromide and dihydropyran gives the (R)-bromo-tetrahydropyranyl ether (VII), which can be oxidized to (VIII) with silver benzoate. The reaction of (VIII) with sodium dimethylsulfoxonium methylide in THF gives the epoxide (IX), which is opened with sodium 1,2,4-triazole (X) to yield the semi-protected diol (XI). Hydrolysis of (XI) in acidic medium affords the diol (XII), which is treated with methanesulfonyl chloride and triethylamine to afford the mono methanesulfonyl ester (XIII). The reaction of (XIII) with sodium methyl mercaptane gives the thioether (XIV), which is finally oxidized with peracetic acid.