反応 #1702093

反応方程式

MeMgBr

Oxaloyl chloride

(2-benzyloxycarbonylamino-ethyl)-phosphonic acid monoethyl ester

DMF

MeMgBr

→

(2-Benzyloxycarbonylamino-ethyl)-methyl-phosphinic acid ethyl ester

溶媒

toluene

THF

CH2Cl2

CH2Cl2

THF

反応条件

後処理

1. 1
   その他reaction mixture
2. 2
   濃縮The reaction was concentrated in vacuo
3. 3
   その他to yield an orange-brown oil that
4. 4
   その他was placed under high vacuum overnight
5. 5
   温度cooled to −30° C.
6. 6
   workup.ADDITIONwas then slowly added to the reaction
7. 7
   その他at about −30° C
8. 8
   workup.STIRRINGThe mixture was stirred at −30° C. for 45 minutes
9. 9
   workup.STIRRINGAfter stirring at −30° C. for another 45 minutes the reaction
10. 10
    その他was quenched by the addition of saturated NH4Cl
11. 11
    温度The reaction was warmed to room temperature
12. 12
    その他partitioned between EtOAc and H2O
13. 13
    その他The layers were separated
14. 14
    洗浄the organic layer was washed with brine
15. 15
    乾燥dried over Na2SO4

実験手順

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.

出典