反应详情

Oxaloyl chloride (2.88 mL, 33 mmol) was dissolved in CH2Cl2 (42 mL). DMF (284 □L) was added to this solution in a drop-wise manner. After 15 minutes a solution of (2-benzyloxycarbonylamino-ethyl)-phosphonic acid monoethyl ester (4.75 g, 16.5 mmol) in solution with CH2Cl2 (42 mL) was added drop-wise over 20 minutes at room temperature. The reaction was stirred at room temperature for 40 minutes. The reaction was determined to be complete by the absence of starting material in a 31P NMR spectrum of the crude reaction mixture. The reaction was concentrated in vacuo to yield an orange-brown oil that was placed under high vacuum overnight. The oil was then dissolved in THF (80 mL) and cooled to −30° C., as determined by an internal thermometer. A 1M solution of MeMgBr in a mixture of toluene and THF was then slowly added to the reaction while keeping the internal temperature at about −30° C. The mixture was stirred at −30° C. for 45 minutes and then another 1 equivalent of MeMgBr was added. After stirring at −30° C. for another 45 minutes the reaction was quenched by the addition of saturated NH4Cl. The reaction was warmed to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the organic layer was washed with brine and dried over Na2SO4. (2-Benzyloxycarbonylamino-ethyl)-methyl-phosphinic acid ethyl ester was isolated from the concentrated filtrate (1.33 g, 28%) by silica gel column chromatography (EtOAc/hexanes then MeOH/CH2Cl2) as a yellow crystalline solid.

1. customreaction mixture
2. concentrationThe reaction was concentrated in vacuo
3. customto yield an orange-brown oil that
4. customwas placed under high vacuum overnight
5. temperaturecooled to −30° C.
6. additionwas then slowly added to the reaction
7. customat about −30° C
8. stirringThe mixture was stirred at −30° C. for 45 minutes
9. stirringAfter stirring at −30° C. for another 45 minutes the reaction
10. customwas quenched by the addition of saturated NH4Cl
11. temperatureThe reaction was warmed to room temperature
12. custompartitioned between EtOAc and H2O
13. customThe layers were separated
14. washthe organic layer was washed with brine
15. dry with materialdried over Na2SO4