1,4-Dioxane → HCID 68153582, compound

HRID 2039382Notes

Reaction equation

HRID 2039382 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:18]([O:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[C:23]([F:30])[C:22]=1[F:31])[CH3:19].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[CH2:18]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]3[CH2:17][CH2:16][C:11]4([O:15][CH2:14][CH2:13][O:12]4)[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)=[C:23]([F:30])[C:22]=1[F:31])[CH3:19]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 100858501,4-Dioxaspiro[4.5]dec-7-ene, 8-(4-bromophenyl)-HCID 15135235B-(4-Ethoxy-2,3-difluorophenyl)boronic acid

Product 1

HCID 68153582HCID 68153582, compoundYield 75.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

8-(4-Bromophenyl)-1,4-dioxaspiro(4.5)dec-7-ene (s71) (30.0 g), 4-ethoxy-2,3-difluorophenylboronic acid (s70) (24.6 g), potassium phosphate (K3PO4; 64.7 g), dichlorobistriphenylphosphine palladium (II) (Pd(Ph3P)2Cl2; 2.1 g) and 1,4-dioxane (300 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and heated to reflux for 2 hours. After the reaction mixture had been cooled to 25° C., it 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. Pd/C (1.5 g) was added to the purified product, and the mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption had ceased. After the reaction had been completed, Pd/C was removed, and then solvent was distilled off. 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 toluene and heptane (toluene:heptane=1:1 by volume) to give 8-(4′-ethoxy-2′,3′-difluoro-(1,1′-biphenyl)-4-yl)-1,4-dioxaspiro(4.5)decane (s72) (28.8 g). The yield based on the compound (s71) was 75.7%.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  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. additionPd/C (1.5 g) was added to the purified product
  9. customPd/C was removed
  10. distillationsolvent was distilled off
  11. customThe residue was purified by column chromatography with toluene as an eluent
  12. customsilica gel as a stationary phase powder, and then by recrystallization from a mixed solvent of toluene and heptane (toluene:heptane=1:1 by volume)

Sources & evidence

ORD record
ord-084d43ba879d4f0fa52fad978dfb889c
Source dataset
uspto-grants-2013_11
Patent number
US08580146B2

Reaction notes

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