Diethyl methylphosphonate → HCID 11214188, compound

Participants

Reaction Conditions

Reaction Steps

A 4-necked, round bottomed flask, equipped with a mechanical stirrer, digital thermometer, nitrogen inlet-outlet and a condenser is charged with methanphosphonic acid diethyl ester (4.65 g, 30.59 mmol) and tetrahydrofuran (11 mL). The solution is cooled down to −78° C. and butyllithium (15.3 mL of a 1.6 M solution in hexane, 24.47 mmol) is added. After stirring for additional 60 min at −78° C., a solution of (S)-3-(tert-butyl-dimethyl-silanyloxy)-pentanedioic acid methoxy-methyl-amide-((S)-1-phenyl-ethyl)amide (2.5 g) in tetrahydrofuran (10 mL) is added to the reaction mixture while maintaining the temperature at −78° C. Stirring is continued for 1 h at this temperature and the reaction is quenched by slow addition of a solution of acetic acid (1.84 g) in tetrahydrofuran (1.25 ml) at −78° C. The reaction mixture is then allowed to warm up to room temperature and poured onto ethyl acetate (125 mL) and brine (125 mL). The biphasic mixture is stirred for 10 min and the organic layer is separated. The water layer is extracted with ethyl acetate. The organic layers are combined, washed with water, dried over anhydrous magnesium sulfate and the solvent is evaporated in vacuo to obtain the crude [(R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-oxo-5-((S)-1-phenyl-ethylcarbamoyl)-pentyl-phosphonic acid diethyl ester as a viscous oil. The crude product is purified by column chromatography with ethyl acetate/hexane (1:1) as eluent to obtain [(R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-oxo-5-((S)-1-phenyl-ethylcarbamoyl)-pentyl]-phosphonic acid diethyl ester as a highly viscous oil. [α]D20=−40.2° (CHCl3, c=1); MS (ES+, m/z): 522 ([M+Na]+, 100%); IR(Film): strong absorbtions at 3297, 2930, 1717, 1652, 1542, 1254, 1026, 837 cm−1.

Provenance & Evidence