Water → HCID 131729505, compound

HRID 1095257Notes

Reaction equation

HRID 1095257 reaction equation
[F:1][C:2]1[C:7]([F:8])=[C:6]([CH:9]2[CH2:14][CH2:13][CH:12](CCCCC)[CH2:11][CH2:10]2)[CH:5]=[CH:4][C:3]=1[CH:20]1[CH2:25][CH2:24][CH:23](C2CCC(O)CC2)[CH2:22][CH2:21]1.[H-].[Na+].Br[CH2:36][CH3:37].[OH2:38]>CN(C)C=O.C1(C)C=CC=CC=1>[F:8][C:7]1[C:2]([F:1])=[C:3]([CH:20]2[CH2:21][CH2:22][CH:23]([CH2:13][CH2:14][CH2:9][CH2:10][CH3:11])[CH2:24][CH2:25]2)[CH:4]=[CH:5][C:6]=1[C:9]1([CH:7]2[CH2:2][CH2:3][CH:4]([O:38][CH2:36][CH3:37])[CH2:5][CH2:6]2)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1

Participants

7

Reactant 4

HCID 962WaterHCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 66781618HCID 66781618, compound

Product 1

HCID 131729505HCID 131729505, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

4′-(2,3-Difluoro-4-(4-pentylcylohexyl)phenyl)bi(cyclohexane)-4-ol (48) (5.0 g) synthesized according to the method described in Example 7, sodium hydride (0.59 g) and dimethylformamide (50 ml) were put in a reaction vessel under a nitrogen atmosphere, and heated to 60° C. The mixture was stirred for 1 hour, then bromoethane (49) (1.34 g) dissolved in dimethylformamide (10 ml) was added dropwise thereto, and the mixture was heated to 120° C. The stirring was continued for 2 hours, and cooled slowly to room temperature, and then water (200 ml) and toluene (200 ml) were added and mixed thereto. The mixture was then allowed to stand until it had separated into two phases, the organic and aqueous phases, and an extractive operation to an organic phase was carried out. The organic phase was fractionated, and washed sequentially with water and a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was purified with a fractional operation by means of column chromatography using a mixed solvent of toluene and heptane (toluene:heptane=2:1 by volume) as an eluent and silica gel as a stationary phase powder, and further purified by means of recrystallization from a mixed solvent of heptane and Solmix (heptane: Solmix=1:1 by volume), and dried, giving 3.2 g of 4-(2,3-difluoro-4-(4-pentylcyclohexyl)phenyl-4′-ethoxybi(cyclohexane) (No. 168). The yield based on the compound (48) was 59.5%.

Workup

  1. customwere put in a reaction vessel under a nitrogen atmosphere
  2. additionwas added dropwise
  3. temperaturethe mixture was heated to 120° C
  4. waitThe stirring was continued for 2 hours
  5. temperaturecooled slowly to room temperature
  6. additionmixed
  7. customhad separated into two phases
  8. washwashed sequentially with water
  9. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate
  10. concentrationThe solution was concentrated under reduced pressure
  11. customthe residue was purified with a fractional operation by means of column chromatography
  12. customsilica gel as a stationary phase powder, and further purified by means of recrystallization from a mixed solvent of heptane and Solmix (heptane: Solmix=1:1 by volume)
  13. customdried

Sources & evidence

ORD record
ord-264c118991464ce3aeb100e759dfafe1
Source dataset
uspto-grants-2012_03
Patent number
US08137583B2

Reaction notes

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