4-(2-fluorobenzyloxy)-N-methyl-N-methoxybenzamide → 1-(4-[2-Fluorobenzyloxy]phenyl)-2-propen-1-one

Temperature

-78 °C

4-(2-fluorobenzyloxy)-N-methyl-N-methoxybenzamide (P3, 6.0 g, 20.7 mmol) was dissolved in THF (100 mL) and cooled to −78° C. A 1.0 M solution of vinyl magnesium bromide in THF (31 mL, 31 mmol) was added and the cold bath was removed. Upon warming to 20-25° C., the mixture was poured into a vigorously stirred solution of 1 M HCl. The resulting mixture was extracted twice with CH2Cl2. The combined organic layers were then washed with 1 M HCl, then with a saturated NaHCO3 solution, dried over Na2SO4, and concentrated to a thick residue. The product was purified by flash column chromatography eluting with 0→40% acetone hexanes (gradient). Concentration of the fractions containing 4 gave an oil that crystallized upon standing (4.83 g, 91% yield).

1. customthe cold bath was removed
2. temperatureUpon warming to 20-25° C.
3. additionthe mixture was poured into a vigorously stirred solution of 1 M HCl
4. extractionThe resulting mixture was extracted twice with CH2Cl2
5. washThe combined organic layers were then washed with 1 M HCl
6. dry with materialwith a saturated NaHCO3 solution, dried over Na2SO4
7. concentrationconcentrated to a thick residue
8. customThe product was purified by flash column chromatography
9. washeluting with 0→40% acetone hexanes (gradient)
10. additionConcentration of the fractions containing 4
11. customgave an oil that
12. customcrystallized

ORD record

ord-7b88ed6651f04a88861bfad3f34fbdcf

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759542B2