Trisodium phosphate dodecahydrate → 4'-n-Propyl-3,5-difluoro-biphenyl-4-ylamine

HRID 413620

Reaction equation

HRID 413620 reaction equation
O.O.O.O.O.O.O.O.O.O.O.O.P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].Br[C:22]1[CH:28]=[C:27]([F:29])[C:25]([NH2:26])=[C:24]([F:30])[CH:23]=1.[CH2:31]([C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)[CH2:32][CH3:33]>O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:31]([C:34]1[CH:39]=[CH:38][C:37]([C:22]2[CH:28]=[C:27]([F:29])[C:25]([NH2:26])=[C:24]([F:30])[CH:23]=2)=[CH:36][CH:35]=1)[CH2:32][CH3:33]

Participants

6

Reactant 3

HCID 61473Trisodium phosphate dodecahydrateHCID 6101914-Bromo-2,6-difluoroanilineHCID 4100861(4-Propylphenyl)boronic acid

Product 1

HCID 700099564'-n-Propyl-3,5-difluoro-biphenyl-4-ylamineYield 99.5%

Reagents, catalysts & solvents 2

HCID 10122028Bis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Procedure

348 g trisodiumphosphate dodecahydrate (Merck KGaA, Art. No.106 578) were dissolved in 500 ml of distilled water. Then 8.563 g bis(triphenylphosphine) palladium (Merck KGaA, Art. No. 804 174) and 0.611 g hydaziniumhydroxide (Merck KGaA, Art. No. 804 604) were added. The suspension was stirred for 5 minutes. Then, 126.886 g 4-bromo-2,6-difluoro-aniline, prepared in house, were added. Next 100 g of the p-n-propylphenyl boronic acid, prepared as described above, dissolved in 600 ml dried tetrahydrafurane (Merck KGaA, Art. No.108 107) was added dropwise. The reaction mixture was heated 6 hours under reflux. The organic layer was separated, dried over Na2SO4 and it's solvent evaporated. The isolated crude product (150 g of 4′-n-propyl-3,5-difluoro-biphenyl-4-ylamine was used for the next step of the reaction without further purificatoin.

Workup

  1. addition804 604) were added
  2. additionwere added
  3. dissolutiondissolved in 600 ml
  4. customdried tetrahydrafurane (Merck KGaA, Art. No.108 107)
  5. additionwas added dropwise
  6. temperatureThe reaction mixture was heated 6 hours
  7. temperatureunder reflux
  8. customThe organic layer was separated
  9. dry with materialdried over Na2SO4
  10. customevaporated

Sources & evidence

ORD record
ord-4abd16b979e747879e943d62a7d5e4d7
Source dataset
uspto-grants-2003_05
Patent number
US06569505B2

Linked notes

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