反应详情

3,5-Trans-N-(2-fluorobenzyl)-1-(N-benzyloxycarbonylpiperidin-4-yl-methyl)-5-(3-tert-butoxycarbonylaminomethylphenyl)-7-chloro-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetamide (1) In methanol (20 ml) were dissolved 2-amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol produced in Example 1-(2) (1.0 g) and N-benzyloxycarbonyl piperidine-4-carbaldehyde (0.82 g), followed by addition of acetic acid (0.2 g). To the mixture was added, while stirring at room temperature, cyano sodium borohydride (0.2 g). The reaction mixture was stirred for 30 minutes at 60° C., which was then concentrated. To the concentrate was added water (40 ml), followed by extraction with ethyl acetate (60 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-(N-benzyloxycarbonylpiperidin-4-yl-methyl)amino-5-chloro-α-(3-tert-butoxycarbonylaminomethylphenyl)benzyl alcohol (1.5 g) as a colorless oily product.

1. additionTo the mixture was added
2. stirringThe reaction mixture was stirred for 30 minutes at 60° C.
3. concentrationwhich was then concentrated
4. additionTo the concentrate was added water (40 ml)
5. extractionfollowed by extraction with ethyl acetate (60 ml)
6. washThe organic layer was washed with water
7. dry with materialdried over anhydrous sodium sulfate
8. distillationThe solvent was distilled off
9. customthe residue was purified by means of a silica gel column chromatography