Water → 1-(4-Ethoxy-2,3-difluorophenyl)-4-methoxymethylenecyclohexane

温度

-30 °C

Well-dried methoxymethyltriphenylphosphonium chloride (166.1 g) was mixed with THF (500 ml) under an atmosphere of nitrogen, and the solution was cooled to −30° C. Potassium t-butoxide (t-BuOK; 54.4 g) was added in two portions in the temperature range of −30° C. to −20° C. After 30 minutes of stirring at −20° C., the compound (s9) (102.7 g) dissolved in THF (100 ml) was added dropwise in the temperature range of −30 to −20° C. After 30 minutes of stirring at −10° C., the reaction mixture was treated with water, and the aqueous layer was extracted with toluene. The combined organic layers were washed with water, and then dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure. The residue was purified by column chromatography with a mixed solvent of heptane and toluene (heptane:toluene=1:1 by volume) as an eluent and silica gel as a stationary phase powder to give 1-(4-ethoxy-2,3-difluorophenyl)-4-methoxymethylenecyclohexane. The compound was mixed with formic acid (87%; 55.8 g) and toluene (300 ml), and the mixture was heated to reflux for 2 hours. After the reaction mixture had been cooled to 30° C., it was treated with water, and the aqueous layer was extracted with toluene. The combined organic layers were washed with water, a saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography with toluene as an eluent and silica gel as a stationary phase powder, and then by recrystallization from a mixed solvent of heptane and toluene (heptane:toluene=2:1 by volume) to give trans-4-(4-ethoxy-2,3-difluorophenyl)-cyclohexanecarboxaldehyde (s10) (54.6 g). The yield based on the compound (s9) was 50.4%.

1. additionwas added dropwise in the temperature range of −30 to −20° C
2. stirringAfter 30 minutes of stirring at −10° C.
3. extractionthe aqueous layer was extracted with toluene
4. washThe combined organic layers were washed with water
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationThe solution was concentrated under reduced pressure
7. customThe residue was purified by column chromatography with a mixed solvent of heptane and toluene (heptane:toluene=1:1 by volume) as an eluent

ORDレコード

ord-be8072dd9b5449ee87ffad5b35b9df2b

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08580146B2