Phosphoric acid, disodium salt, dodecahydrate → 2-(3,5-Difluoro-4'-propylbiphenyl-4-yl)-5-propylthiophene

HRID 449733Notes

Reaction equation

HRID 449733 reaction equation
Br[C:2]1[S:3][C:4]([CH2:7][CH2:8][CH3:9])=[CH:5][CH:6]=1.[CH2:10]([C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[C:23]([F:25])[C:22](B(O)O)=[C:21]([F:29])[CH:20]=2)=[CH:15][CH:14]=1)[CH2:11][CH3:12].P([O-])(O)(O)=O.[Na+].O.O.O.O.O.O.O.O.O.O.O.O.P([O-])([O-])(O)=O.[Na+].[Na+]>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:25][C:23]1[CH:24]=[C:19]([C:16]2[CH:17]=[CH:18][C:13]([CH2:10][CH2:11][CH3:12])=[CH:14][CH:15]=2)[CH:20]=[C:21]([F:29])[C:22]=1[C:2]1[S:3][C:4]([CH2:7][CH2:8][CH3:9])=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 61456Phosphoric acid, disodium salt, dodecahydrateHCID 218019042-Bromo-5-propylthiopheneHCID 23672064Monosodium phosphateHCID 580284314'-Propyl-3,5-difluoro-4-biphenylboronic acid

Product 1

HCID 580284282-(3,5-Difluoro-4'-propylbiphenyl-4-yl)-5-propylthiophene

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

5.0 g (24.4 mmol) of 2-bromo-5-propylthiophene, 7.40 g (26.8 mmol) of 4′-propyl-3,5-difluoro-4-biphenylboronic acid and 2.82 g (2.44 mmol) of tetrakis(triphenylphosphine)palladium(0) are initially introduced in 160 ml of toluene. A solution of 5.85 g (48.8 mmol) of sodium dihydrogenphosphate and 13.8 g (97.5 mmol) of disodium hydrogenphosphate dodecahydrate in 50 ml of water is added, and the mixture is heated under reflux for 19 h. After cooling, the organic phase is separated off, and the aqueous phase is extracted a number of times with toluene. The combined organic phases are washed with water and sat. sodium chloride soln. The solution is dried using sodium sulfate and concentrated to completion. The residue is purified by column chromatography (SiO2, n-heptane). Further purification is carried out by recrystallisation from ethanol and n-heptane; 2-(3,5-difluoro-4′-propylbiphenyl-4-yl)-5-propylthiophene (PUS-3-3) is obtained as a colourless solid (m.p. 64° C.).

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 19 h
  3. temperatureAfter cooling
  4. customthe organic phase is separated off
  5. extractionthe aqueous phase is extracted a number of times with toluene
  6. washThe combined organic phases are washed with water and sat. sodium chloride soln
  7. customThe solution is dried
  8. concentrationconcentrated to completion
  9. customThe residue is purified by column chromatography (SiO2, n-heptane)
  10. customFurther purification
  11. customis carried out by recrystallisation from ethanol and n-heptane

Sources & evidence

ORD record
ord-acd01aa93ada466a888862727f9330f4
Source dataset
uspto-grants-2013_07
Patent number
US08486297B2

Reaction notes

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