Trimethyl phosphonoacetate → HCID 18467805, compound

Temperature

-78 °C

2,5-Dimethyl-3-oxo-2-tetrahydrofuroic acid, t-butyl ester (64 mg, from Reference Example 23, Step D) was dissolved in anhydrous methanol (1 mL) and cooled to −78° C. Potassium bis(trimethylsilyl)amide 0.66 mL) was added dropwise over 10 minutes. After being stirred at 78° C. for 15 minutes, trimethyl phosphonoacetate (65 mg, dissolved in 1.5 mL tetrahydrofuran) was added dropwise over 25 minutes. Upon completion of addition, the cold bath was removed and the mixture was allowed to stir at room temperature for 3 h when TLC (4/1 hexane/ethyl acetate) showed formation of a new spot. At 0° C., the reaction was quenched by addition of 1.5 mL of saturated aqueous ammonium chloride and the product was extracted with ethyl acetate twice, washed with saturated sodium chloride and dried over anhydrous magnesium sulfate. The crude product obtained after filtration and removal of volatiles was flash chromatographed over silica get, using gradient elution (50-10/1 hexane/ethyl acetate) to give 31 mg of the desired compound, homogeneous by TLC (Rf=0.5 in 4/1 hexane/ethyl acetate). The NMR showed that all the diastereomers are present in this sample.

1. additionUpon completion of addition
2. customthe cold bath was removed
3. stirringto stir at room temperature for 3 h when TLC (4/1 hexane/ethyl acetate)
4. customAt 0° C., the reaction was quenched by addition of 1.5 mL of saturated aqueous ammonium chloride
5. extractionthe product was extracted with ethyl acetate twice
6. washwashed with saturated sodium chloride
7. dry with materialdried over anhydrous magnesium sulfate
8. customThe crude product obtained
9. filtrationafter filtration and removal of volatiles
10. customchromatographed over silica
11. customget
12. washelution (50-10/1 hexane/ethyl acetate)

ORD record

ord-1fddb71be52440789487a484166d1ed0

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06420418B1