Stereoselective synthesis of (±)-threo-2-amino-1-(4-nitrophenyl)-1,3-propanediol

Abstract

Addition of hypobromic acid to styrene afforded styrene bromohydrin (I) which was dehydrated to ω-bromostyrene (II). Prince reaction of II with aqueous formaldehyde gave 5-bromo-4-phenyl-1,3-dioxane (III). The bromine atom in III was replaced with amino group by treatment with methanolic ammonia at 150°C and 6–8 MPa and the obtained threo-5-amino-4-phenyl-1,3-dioxane (IVa) was hydrolyzed to give (±)-threo-2-amino-1-phenyl-1,3-propanediol (V). Suitably chosen method of nitration converted the free base IVa or its N-acetyl derivative IVb into 5-amino-4-(4-nitrophenyl)-1,3-dioxane (VIa) or its N-acetyl derivative VIb which without isolation were hydrolyzed to threo-2-amino-1-(4-nitrophenyl)-1,3-propanediol (VII), isolated as hydrochloride. The liberated base was resolved into enantiomers and dichloracetylated in the known manner to give D-(-)-threo-2-dichloracetylamino-1-(4-nitrophenyl)-1,3-propanediol (chloramphenicol).