反应详情

1.73 g. (6 mmol) Methanediphosphonic acid tetraethyl ester is added dropwise to 144 mg. (6 mmol) sodium hydride in 5 ml. anhydrous toluene. After completion of the evolution of hydrogen, stirring is continued for 30 minutes and then 1.7 g. (6 mmol) N-(2-bromoethoxyethyl)-phthalimide (m.p. 83°-85° C.) is added dropwise thereto. The reaction mixture is stirred for 24 hours at ambient temperature, then mixed with water, the aqueous phase is adjusted to pH 5 with 2N hydrochloric acid and the organic phase is separated off, dried and evaporated. The residue is purified over 250 g. silica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g. (12% of theory) 5-phthalimido-3-oxapentane-1,1-diphosphonic acid tetraethyl ester in the form of an oily substance. The ester is subsequently boiled under reflux for 12 hours with 10 ml. 6N hydrochloric acid and, after cooling, the precipitated phthalic acid is filtered off with suction. The residue is taken up in water, the solution is adjusted with 2N aqueous sodium hydroxide solution to pH 5 and mixed, while cooling with ice, with a large excess of methanol. The precipitate obtained is filtered off with suction and dried. There is obtained 0.125 g. (7.2% of theory) of the desired compound in the form of the monosodium salt containing 1 mole water of crystallisation; m.p.>300° C.; Mrel =0.30.

1. customthe organic phase is separated off
2. customdried
3. customevaporated
4. customThe residue is purified over 250 g
5. customsilica gel (elution agent: methylene chloride/methanol 4/1 v/v) to give 0.35 g
6. temperatureunder reflux for 12 hours with 10 ml
7. filtrationthe precipitated phthalic acid is filtered off with suction
8. additionmixed
9. temperaturewhile cooling with ice
10. customThe precipitate obtained
11. filtrationis filtered off with suction
12. customdried
13. customThere is obtained 0.125 g