Triphenylphosphine → Rac.-n-[2,6-dimethyl-4-[[[3-[[(1,1-dimethylethyl) dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

Temperatur

0 °C

Triphenylphosphine (0.762 g, 2.9 mmol) was added to a suspension of 2,6-dimethyl-4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoic acid (Example 111; 1 g, 2.42 mmol) in dichloromethane (12 mL) at 25° C. The mixture was cooled to 0° C. and N-chlorosuccinimide (0.387 g, 2.9 mmol) was added. After stirring 15 min at 0° C., the mixture was stirred for an additional 15 min at 25° C. and then a solution of rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (1.99 g, 6 mmol) in dichloromethane (2 mL) was added in one portion. The reaction was stirred for 5 h (a precipitate formed at 2 h), then was filtered and the solids were washed with dichloromethane and discarded. The filtrate was washed with 1N hydrochloric acid solution (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL), then was dried (MgSO4) and concentrated under reduced pressure. The residue was flash chromatographed (silica gel, 10% ethyl acetate in petroleum ether) to yield rac.-N-[2,6-dimethyl-4-[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzyl]amino]carbonyl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (1.33 g, 93% yield) as a colorless foam.

1. stirringthe mixture was stirred for an additional 15 min at 25° C.
2. additionwas added in one portion
3. stirringThe reaction was stirred for 5 h (a precipitate
4. customformed at 2 h),
5. filtrationthen was filtered
6. washthe solids were washed with dichloromethane
7. washThe filtrate was washed with 1N hydrochloric acid solution (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL)
8. dry with materialwas dried (MgSO4)
9. concentrationconcentrated under reduced pressure
10. customchromatographed (silica gel, 10% ethyl acetate in petroleum ether)

ORD-Eintrag

ord-b69b0d92db76422b975afe4b1a0428ec

Quelldatensatz

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06515124B2