tert-Butyl acetate → 4-Cyano-5-(6-ethoxy-2'-fluoro-4-nitro-biphenyl-3-yl)-3-(tetrahydro-pyran-4-yl)-pent-4-enoic acid tert-butyl ester

Temperatur

-78 °C

To a solution of tert-butyl acetate (217 μL, 1.6 mmol) in THF (0.92 mL) at −78° C., LHMDS (1.0 M in THF, 1.4 mL) was added slowly. After 30 min of stirring at −78° C., [1-cyano-2-(tetrahydro-pyran-4-yl)-vinyl]-phosphonic acid diethyl ester (302 mg, 1.1 mmol) dissolved in THF (0.92 mL) was added, followed by CuI (6.3 mg, 0.03 mmol). The resulting solution was warmed to room temperature, stirred for 2 h, and then 6-ethoxy-2′-fluoro-4-nitro-biphenyl-3-carbaldehyde (266.0 mg, 0.9195 mmol), prepared as in Step C above, was added. The resulting solution was stirred at room temperature for another 20 h. Ethyl acetate was then added, and the resulting solution was washed with hydrochloric acid solution (1.0 M) two times and with brine one time, and then dried over magnesium sulfate. The resulting solution was filtered and concentrated. The residue was purified on a silica gel column eluted with a solvent mixture of ethyl acetate and heptanes from 0:100 to 25:75 to yield a residue.

1. additionwas added
2. temperatureThe resulting solution was warmed to room temperature
3. stirringstirred for 2 h
4. additionwas added
5. stirringThe resulting solution was stirred at room temperature for another 20 h
6. washthe resulting solution was washed with hydrochloric acid solution (1.0 M) two times and with brine one time
7. dry with materialdried over magnesium sulfate
8. filtrationThe resulting solution was filtered
9. concentrationconcentrated
10. customThe residue was purified on a silica gel column
11. washeluted with a solvent mixture of ethyl acetate and heptanes from 0:100 to 25:75
12. customto yield a residue

ORD-Eintrag

ord-6cf81ea46b3f48ae84baecb516740ad1

Quelldatensatz

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07786116B2