反应详情

To the compound 97 (1.74 g) in an acetic acid (35 ml) suspension, zinc powder (3.5 g) was added, and the mixture was stirred at room temperature for 4 hours. The insolubles were filtered out and the filtrate was concentrated in vacuo. To the residue, acetic acid (20 ml) was added, the mixture was stirred at 60° C. for 1 hour, then the insolubles were filtered out. The filtrate was concentrated in vacuo, the residue was diluted with chloroform-methanol-acetic acid (5:1:0.1) (20 ml), and tha mixture was stirred at room temperature for 1 hour. The insolubles were collected by filtration, then ethyl acetate (105 ml), saturated aqueous ammonium chloride solution (105 ml), and water (53 ml) were added to the obtained crystals, and the mixture was stirred at room temperature for 4 hours. The layers were separated, and the aqueous layer was extracted with ethyl acetate (50 ml×2). The organic layer and the extract were combined, then the mixture was washed with brine, dried over sodium sulfate, then concentrated. The residue was purified by flash column chromatography (silica gel, chloroform/ethyl acetate/methanol=50/50/5 to 50/50/10) to obtain 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3-(hydroxyimino)-7-oxo-1,4-diazepan-1-yl]carbonyl}amino)butyl]benzoic acid (compound 14) (1.07 g).

1. filtrationThe insolubles were filtered out
2. concentrationthe filtrate was concentrated in vacuo
3. additionTo the residue, acetic acid (20 ml) was added
4. stirringthe mixture was stirred at 60° C. for 1 hour
5. filtrationthe insolubles were filtered out
6. concentrationThe filtrate was concentrated in vacuo
7. additionthe residue was diluted with chloroform-methanol-acetic acid (5:1:0.1) (20 ml)
8. stirringtha mixture was stirred at room temperature for 1 hour
9. filtrationThe insolubles were collected by filtration
10. additionethyl acetate (105 ml), saturated aqueous ammonium chloride solution (105 ml), and water (53 ml) were added to the obtained crystals
11. stirringthe mixture was stirred at room temperature for 4 hours
12. customThe layers were separated
13. extractionthe aqueous layer was extracted with ethyl acetate (50 ml×2)
14. washthe mixture was washed with brine
15. dry with materialdried over sodium sulfate
16. concentrationconcentrated
17. customThe residue was purified by flash column chromatography (silica gel, chloroform/ethyl acetate/methanol=50/50/5 to 50/50/10)