The reaction of 2-benzoylbenzoic acid (I) with SOCl2 in CHCl3, benzene or DMF gives the corresponding acyl chloride (II), which is condensed with ethanolamine (III) by means of TEA in CHCl3 to yield the amide (IV). The reduction of (IV) with LiAlH4 in THF affords the diol (V), which is cyclized by means of Ts-OH in refluxing benzene to provide 1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocine (VI). Finally, this compound is methylated by means of dimethyl sulfate in refluxing benzene, or by means of formaldehyde in hot dioxane/water. Alternatively, the cyclization of N-[2-[1-[2-(chloromethyl)phenyl]-1-phenylmethoxy]ethyl]-N-methylamine (VII) by means of pyridine in refluxing acetonitrile gives also the target benzoxazocine.
The reaction of 3-phenylphthalide (I) with N-methylethanolamine (II) in refluxing benzene gives N-(2-hydroxyethyl)-2-(1-hydroxy-1-phenylmethyl)-N-methylbenzamide (III), which is cyclized by means of Ts-OH in refluxing toluene to yield 5-methyl-1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocin-6-one (IV). Finally this compound is reduced with LiAlH4 in refluxing THF to afford the target benzoxazocine. In an alternative method, the reduction of 2-benzoyl-N-(2-hydroxyethyl)-N-methylbenzamide (V) by means of sodium bis(2-methoxyethoxy)aluminum hydride in refluxing toluene gives the diol (VI), which is then cyclized by means of Ts-OH in refluxing toluene, or by means of aq. 48% HBr in hot chloroform to afford the target benzoxazocine.
The reaction of 2-benzoylbenzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which is condensed with 2-(methylamino)acetic acid (III) in benzene to yield the N-(2-benzoylbenzoyl)-N-methylglycine (IV). The reduction of (IV) by means of LiAlH4 in refluxing THF affords the diol (V), which is finally cyclized by means of PPA at 80 C to provide the target benzoxazocine.
The reaction of 2-benzoylbenzoic acid (I) with PCl3 in dichloromethane gives the corresponding acyl chloride (II), which is condensed with N-methylethanolamine (III) by means of TEA In dichloroethane to yield the amide (IV). The reaction of (IV) with PCl3 in dichloroethane affords the 2-chloroethylamide (V), which is reduced with NaBH4 and A-OH in dichloromethane to provide the diol (VI). Finally, this compound is cyclized by means of aq. HBr in dichloroethane to give the target benzoxazocine.