2-(1,3-Dioxan-2-yl)ethyltriphenylphosphonium bromide → 2-(2-(4-(2,3-Difluoro-4-ethoxyphenyl)cyclohexylidene)-ethyl)-1,3-dioxane

Temperature

-30 °C

A mixture of 2-(1,3-dioxane-2-yl)-ethyltriphenyl phosphonium bromide (60.4 mmol) and 30 ml of THF was cooled down to −30° C. by use of a refrigerant under a nitrogen flow. To this mixture, t-BuOK (60.4 mmol) was added, and the mixture was stirred for one hour. A solution of the crude 4-(2,3-difluoro-4-ethoxyphenyl)-cyclohexanone (50.3 mmol) dissolved in 100 ml of THF was added dropwise to this mixture while temperature was maintained at −30° C. or below. After completion of the addition, the reaction temperature was gradually elevated to room temperature, and the mixture was stirred for 2 hours. The reaction mixture was filtered with celite, the solvent was distilled off under reduced pressure, the residue was subjected to silica gel column chromatography (eluent: a mixed solvent of ethyl acetate/toluene=3/7), the solvent was distilled off under reduced pressure, and the product was re-crystallized from heptane to form 2-(2-(4-(2,3-difluoro-4-ethoxyphenyl)cyclohexylidene)-ethyl)-1,3-dioxane (36.9 mmol).

1. additionwas added dropwise to this mixture while temperature
2. temperaturewas maintained at −30° C. or below
3. additionAfter completion of the addition
4. customwas gradually elevated to room temperature
5. stirringthe mixture was stirred for 2 hours
6. filtrationThe reaction mixture was filtered with celite
7. distillationthe solvent was distilled off under reduced pressure
8. distillationa mixed solvent of ethyl acetate/toluene=3/7), the solvent was distilled off under reduced pressure
9. customthe product was re-crystallized from heptane

ORD record

ord-4ff8dfbed6ca40f0b866cec334ac483f

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07081279B2