反应详情

2.83 g (6.5 mmol) of compound (A) are dissolved in 100 ml of abs. DMF under argon. 468 mg (19.5 mmol) of sodium hydride are added, and the mixture is stirred at RT for 30 min. Then 7.6 g (19.5 mmol) of Example 10A, dissolved in 10 ml of DMF, are added. Stirring is continued at RT for a further 15 min and the batch is then admixed with 20 ml of water added gradually. Thereafter the batch is concentrated and the residue is stirred up with 150 ml of saturated solution of hydrogen chloride in dichloromethane for 1 h, during which the bis-acyl compound initially formed after enolization, with mass M=1141, is cleaved. This is followed by concentrating and the residue is taken up in 700 ml of ethyl acetate and extracted twice with 200 ml each time of 10% sodium carbonate solution. The organic phase is separated off, concentrated and taken up in 30 ml of ethyl acetate and then admixed with 30 ml of diethyl ether. After brief stirring, undissolved residues are filtered off and the organic phase is concentrated. The residue is purified by flash chromatography on silica gel with ethyl acetate/toluene 4:1 as eluent. The appropriate fractions are concentrated and the residue is taken up in 10 ml of ethyl acetate. 100 ml of cold diethyl ether are added and the batch is left to stand at 0° C. for 30 min. After filtration, the residue is treated once more with 100 ml of diethyl ether. After renewed filtration, the filter residue is collected and dried to obtain 1 g (20% of theory) of the compound fully protected at the amino group.

1. additionare added
2. stirringStirring
3. waitis continued at RT for a further 15 min
4. additionadded gradually
5. concentrationThereafter the batch is concentrated
6. stirringthe residue is stirred up with 150 ml of saturated solution of hydrogen chloride in dichloromethane for 1 h, during which the bis-acyl compound
7. custominitially formed after enolization
8. concentrationby concentrating
9. extractionextracted twice with 200 ml each time of 10% sodium carbonate solution
10. customThe organic phase is separated off
11. concentrationconcentrated
12. filtrationAfter brief stirring, undissolved residues are filtered off
13. concentrationthe organic phase is concentrated
14. customThe residue is purified by flash chromatography on silica gel with ethyl acetate/toluene 4:1 as eluent
15. concentrationThe appropriate fractions are concentrated
16. addition100 ml of cold diethyl ether are added
17. waitthe batch is left
18. waitto stand at 0° C. for 30 min
19. filtrationAfter filtration
20. additionthe residue is treated once more with 100 ml of diethyl ether
21. filtrationfiltration
22. customthe filter residue is collected
23. customdried
24. customto obtain 1 g (20% of theory) of the compound