反应详情

8.63 g (15.2 mmol) of 10-(N-benzyloxycarbonylamino)-4-diisopropylphosphonomethyl-2-formylamino-dec-3-enoic acid ethyl ester are dissolved in 22 ml of dichloromethane, and 9.82 ml (75.9 mmol) of trimethylbromosilane are added dropwise at room temperature. The mixture is stirred at room temperature for 22 hours, 22 ml of absolute ethanol are then added dropwise, and the mixture is stirred for a further 22 hours and concentrated by evaporation in a rotary evaporator. 20 ml of toluene are poured over the residue, and the mixture is concentrated by evaporation in vacuo. This operation is repeated a further three times. The resulting pale yellow foam is dissolved in 150 ml of absolute ethanol, and a solution of 7.5 ml of propylene oxide in 7.5 ml of ethanol is added dropwise within a period of 90 minutes. A crystalline suspension forms, which is stirred overnight at room temperature. The product is filtered off and washed with ethanol and ether. Drying under a high vacuum at room temperature yields 4.70 g of crude product in the form of pale yellow crystals. For further purification, the product is stirred with 46 ml of water. After a small amount (0.33 g) of undissolved material has been filtered off, the clear pale yellow filtrate is completely concentrated by evaporation in vacuo. 20 ml of ethanol and 20 ml of toluene are added to the residue, and the mixture is again concentrated to dryness by evaporation. This operation is repeated twice more using toluene. After drying under a high vacuum, the residue is suspended in 150 ml of absolute ethanol, and a 5-normal solution of hydrogen chloride gas in ethanol is added dropwise, with stirring, until the mixture gives an acid reaction to Congo red. A mixture of 7.4 ml of propylene oxide in 7.4 ml of ethanol is added dropwise to the resulting clear solution within a period of one hour. A crystalline suspension forms, which is stirred for a further 15 hours and then filtered with suction. After washing with ethanol and ether, the product is dried under a high vacuum at 50° for 48 hours, yielding 2.86 g of 2,10-diamino-4-phosphonomethyl-dec-3-enoic acid ethyl ester, which begins to sinter at 157° and melts at 194° with decomposition.

1. stirringthe mixture is stirred for a further 22 hours
2. concentrationconcentrated by evaporation in a rotary evaporator
3. addition20 ml of toluene are poured over the residue
4. concentrationthe mixture is concentrated by evaporation in vacuo
5. dissolutionThe resulting pale yellow foam is dissolved in 150 ml of absolute ethanol
6. additiona solution of 7.5 ml of propylene oxide in 7.5 ml of ethanol is added dropwise within a period of 90 minutes
7. stirringA crystalline suspension forms, which is stirred overnight at room temperature
8. filtrationThe product is filtered off
9. washwashed with ethanol and ether
10. customDrying under a high vacuum at room temperature
11. customyields 4.70 g of crude product in the form of pale yellow crystals
12. customFor further purification
13. stirringthe product is stirred with 46 ml of water
14. filtrationAfter a small amount (0.33 g) of undissolved material has been filtered off
15. concentrationthe clear pale yellow filtrate is completely concentrated by evaporation in vacuo
16. addition20 ml of ethanol and 20 ml of toluene are added to the residue
17. concentrationthe mixture is again concentrated to dryness by evaporation
18. customAfter drying under a high vacuum
19. additiona 5-normal solution of hydrogen chloride gas in ethanol is added dropwise
20. stirringwith stirring, until the mixture
21. customgives
22. additionis added dropwise to the resulting clear solution within a period of one hour
23. stirringA crystalline suspension forms, which is stirred for a further 15 hours
24. filtrationfiltered with suction
25. washAfter washing with ethanol and ether
26. customthe product is dried under a high vacuum at 50° for 48 hours