Diisopropylethylamine → 2-(3-(t-Butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid methyl ester

Temperatur

0 °C

To a solution of 1-(benzyloxycarbonylamino)-2-methylpropyl-phosphonous acid ethyl ester (6.2 g 20.7 mmol) in 150 ml CH2Cl2 was added DIEA (6.5 mL, 47.5 mmol). The mixture solution was cooled down to 0° C. over an ice-water bath. TMSCI (5.5 mL, 42.0 mmol) was added dropwise under N2. The reaction mixture was stirred at ambient temperature for 2 hours, then cooled to 0° C. again. A solution of 2-(3-(t-butoxycarbonylamino)methylphenyl)-propenoic acid methyl ester (6.7 g, 23.0 mmol) in 15 mL CH2Cl2 was added to the reaction mixture. The resulting reaction mixture was stirred at ambient temperature for 18 hours. The reaction was quenched by 10 mL MeOH, then concentrated in vacuo, and the residue was taken up into 300 mL ethyl acetate. The organic phase was washed with 2 N NaHSO4, water, and brine. The solvent was evaporated in vacuo, and the crude product was purified by flash chromatography on silica gel to afford 2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-(benzyloxycarbonyl)amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid methyl ester (10.7 g, 18.1 mmol, 81%) as white solid.

1. additionTMSCI (5.5 mL, 42.0 mmol) was added dropwise under N2
2. temperaturecooled to 0° C. again
3. customThe resulting reaction mixture
4. stirringwas stirred at ambient temperature for 18 hours
5. customThe reaction was quenched by 10 mL MeOH
6. concentrationconcentrated in vacuo
7. washThe organic phase was washed with 2 N NaHSO4, water, and brine
8. customThe solvent was evaporated in vacuo
9. customthe crude product was purified by flash chromatography on silica gel

ORD-Eintrag

ord-a00dc5645ed4413abdf7f55f48c8a688

Quelldatensatz

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08008325B2