Diethyl methylphosphonate → HCID 11214188, compound

Temperature

-78 °C

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.

1. customA 4-necked, round bottomed flask, equipped with a mechanical stirrer
2. temperaturewhile maintaining the temperature at −78° C
3. stirringStirring
4. waitis continued for 1 h at this temperature
5. customthe reaction is quenched by slow addition of a solution of acetic acid (1.84 g) in tetrahydrofuran (1.25 ml) at −78° C
6. temperatureto warm up to room temperature
7. additionpoured onto ethyl acetate (125 mL) and brine (125 mL)
8. stirringThe biphasic mixture is stirred for 10 min
9. customthe organic layer is separated
10. extractionThe water layer is extracted with ethyl acetate
11. washwashed with water
12. dry with materialdried over anhydrous magnesium sulfate
13. customthe solvent is evaporated in vacuo

ORD record

ord-5e702fea95e34e46a67f7dc72ebcd528

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07371865B2