反应详情

A solution of 6.97 g of lithium diisopropylamide in 100 ml of anhydrous tetrahydrofuran is cooled to -78° under an inert atmosphere. With constant stirring, a -78° solution of 10.5 g of ethyl cyclopropylmethyl(methyl)phosphinate in 30 ml of absolute tetrahydrofuran is added over 15-20 minutes via a canula under a positive pressure of inert gas. The resulting pale yellow solution is stirred for 1 hour at -78° and a pre-cooled (-78°) solution of 2.06 g of N-tert.-butoxycarbonyl glycine methyl ester in 20 ml absolute tetrahydrofuran is added over 5-10 minutes via a canula. Chromatographic analysis after 15 minutes stirring at -78° C. indicated the reaction to be complete. At -78° 3.75 ml of glacial acetic acid is added and the mixture allowed to warm to room temperature. The reaction mixture is diluted with dichloromethane and washed with water. Drying of the solvent and removal under reduced pressure affords a pale yellow oil. Removal of the excess starting material by distillation and chromatography of the residue on silica gel gives ethyl 3-(N-tert.-butoxycarbonylamino)-2-oxo-propyl(cyclopropylmethyl)phosphinate as a pale yellow oil; 1H-NMR (CDCl3): δ (ppm)=5.40 (1H, Br t, Exch. D2O, NH), 4.14 (4H, m, CH2OP+CH2N) 3.17 (2H, d, J=17.5 Hz, CH2C=O), 1.93-1.68 (2H, m, PCH2), 1.45 (9H, s, tBu), 1.35 (3H, t, CH3), 0.93 (1H, m, CH), 0.62 (2H, m, CH2), 0.27 (2H, m, CH2).

1. additionis added over 5-10 minutes via a canula
2. stirringChromatographic analysis after 15 minutes stirring at -78° C.
3. customthe reaction
4. washwashed with water
5. customDrying of the solvent and removal under reduced pressure
6. customaffords a pale yellow oil
7. customRemoval of the
8. distillationby distillation and chromatography of the residue on silica gel