Water → HCID 178439058, compound

HRID 2039384Notes

Reaction equation

HRID 2039384 reaction equation
[CH3:1][C:2]([CH3:5])([O-])[CH3:3].[K+].[CH2:7]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3(C=O)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[C:18]([F:30])[C:17]=2[F:31])=[C:12]([F:32])[C:11]=1[F:33])[CH3:8].O>C1COCC1>[CH2:7]([O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C@H:22]3[CH2:27][CH2:26][C@H:25](/[CH:17]=[CH:18]/[CH2:19][CH2:1][C:2]4[CH:5]=[CH:16][C:13]([CH2:12][CH2:11][CH3:10])=[CH:14][CH:3]=4)[CH2:24][CH2:23]3)=[C:18]([F:30])[C:17]=2[F:31])=[C:12]([F:32])[C:11]=1[F:33])[CH3:8]

Participants

5

Reactant 3

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 86668463HCID 86668463, compound

Product 1

HCID 178439058HCID 178439058, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Well-dried compound (s5) (6.4 g) was mixed with THF (100 ml) under an atmosphere of nitrogen, and the solution was cooled to −10° C. Potassium t-butoxide (t-BuOK; 1.4 g) was added in the temperature range of −10° C. to −5° C. After 60 minutes of stirring at −10° C., the compound (s78) (4.0 g) dissolved in THF (30 ml) was added dropwise in the temperature range of −10 to −5° C. After 30 minutes of stirring at 0° 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, and the residue was purified by column chromatography with toluene as an eluent and silica gel as a stationary phase powder. The purified product was mixed with sodium benzenesulfonate dihydrate (20.2 g) and Solmix A-11 (100 ml). Then, 6N-hydrochloric acid (16.8 ml) was added, and the mixture was heated to reflux for 2 hours. The reaction mixture 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 ethyl acetate and Solmix A-11 (ethyl acetate:Solmix=1:4 by volume) to give (E)-4-ethoxy-2,2′,3,3′-tetrafluoro-4′-(trans-4-(4-(4-propylphenyl)but-1-en-1-yl)cyclohexyl)-1,1′-biphenyl (No. 262) (3.6 g). The yield based on the compound (s78) was 65.3%.

Workup

  1. additionwas added dropwise in the temperature range of −10 to −5° C
  2. stirringAfter 30 minutes of stirring at 0° 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 toluene as an eluent
  8. additionThe purified product was mixed with sodium benzenesulfonate dihydrate (20.2 g) and Solmix A-11 (100 ml)
  9. additionThen, 6N-hydrochloric acid (16.8 ml) was added
  10. temperaturethe mixture was heated
  11. temperatureto reflux for 2 hours
  12. additionThe reaction mixture was treated with water
  13. extractionthe aqueous layer was extracted with toluene
  14. washThe combined organic layers were washed with water
  15. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and water, and then dried over anhydrous magnesium sulfate
  16. distillationThe solvent was distilled off under reduced pressure
  17. customthe residue was purified by column chromatography with toluene as an eluent
  18. customsilica gel as a stationary phase powder, and then by recrystallization from a mixed solvent of ethyl acetate and Solmix A-11 (ethyl acetate:Solmix=1:4 by volume)

Sources & evidence

ORD record
ord-3f30d23ee57042a992c022752c6339e4
Source dataset
uspto-grants-2013_11
Patent number
US08580146B2

Reaction notes

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