Trimethyl phosphite → Methyl 4-(dimethoxyphosphoryl)-3-oxobutanoate

Temperature

125 °C

A mixture of the title A compound (83.9 g, 0.378 mol), bissilylacetamide (15.23 g, 0.075 mol) and trimethylphosphite (200 g, 1.61 mol) was refluxed (oil bath temp. 125° C.) under argon for 15 hours. TLC, silica gel, 10 methanol/ethyl acetate Rf =0.39, (UV and 4,4'-bis-dimethylaminobenzhydrol/heat). The reaction mixutre was cooled to 70° C., volatile components were distilled at 10 mm pressure, and then the product was kept at 0.5 mm pressure for ten minutes. The product was taken up in 250 mL ethyl acetate and washed with brine (2×50 mL), aqueous sodium bicarbonate (25 mL, vigorous reaction) and brine. The organic phase was dried (magnesium sulfate) and the solvent was removed under vaccum to give 55.79 g of the crude title compound. The product was heated to 100° C. under vaccum (0.4 mm) for five minutes to remove the more volatile impurities. The product was cooled, dissolved in 200 mL ethyl acetate, and treated with charcoal, and filtered through a pad of Celite. The filtrate was evaporated to give 43.01 g (yield 51% uncorrected) of the title compound

1. temperatureThe reaction mixutre was cooled to 70° C.
2. distillationvolatile components were distilled at 10 mm pressure
3. waitthe product was kept at 0.5 mm pressure for ten minutes
4. washwashed with brine (2×50 mL), aqueous sodium bicarbonate (25 mL, vigorous reaction) and brine
5. dry with materialThe organic phase was dried (magnesium sulfate)
6. customthe solvent was removed under vaccum
7. customto give 55.79 g of the crude title compound
8. temperatureThe product was heated to 100° C. under vaccum (0.4 mm) for five minutes
9. customto remove the more volatile impurities
10. temperatureThe product was cooled
11. dissolutiondissolved in 200 mL ethyl acetate
12. additiontreated with charcoal
13. filtrationfiltered through a pad of Celite
14. customThe filtrate was evaporated

ORD record

ord-e5df68878720484695a76818323c459c

Source dataset

uspto-grants-1994_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05298625