Potassium Phosphate, Tribasic → 4-Amino-3-cyano-6-fluoro-5-methoxy-2-methylbiphenyl

HRID 17303Notes

Reaction equation

HRID 17303 reaction equation
[NH2:1][C:2]1[C:9]([O:10][CH3:11])=[C:8]([F:12])[C:7](Br)=[C:6]([CH3:14])[C:3]=1[C:4]#[N:5].[C:15]1(B(O)O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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>[NH2:1][C:2]1[C:9]([O:10][CH3:11])=[C:8]([F:12])[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:6]([CH3:14])[C:3]=1[C:4]#[N:5]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 860974532-Amino-5-bromo-4-fluoro-3-methoxy-6-methylbenzonitrile

Product 1

HCID 860974414-Amino-3-cyano-6-fluoro-5-methoxy-2-methylbiphenyl

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Under nitrogen atmosphere, 2-amino-5-bromo-4-fluoro-3-methoxy-6-methylbenzonitrile (I-45) (20.0 g, 77.20 mmol), phenylboronic acid (11.3 g, 92.64 mmol), potassium phosphate (34.4 g, 162.11 mmol) were dissolved in a mixed liquid of 1,4-dioxane (400 ml) and water (20 ml), tetrakis(triphenylphosphine)palladium (2.6 g, 2.32 mmol) was added, followed by stirring at 110° C. for 15 hours. After cooling, the insoluble matter was separated by filtration through Celite, the reaction solvent was evaporated away under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with water and saturated brine, the organic layer was dried over anhydrous sodium sulfate, then the solvent was evaporated away under reduced pressure. The resulting residue was subjected to silica gel column chromatography, eluted wrath a mixed solvent of n-hexane/ethyl acetate (3:1, v/v) to obtain the entitled compound (20.12 g, quant) as a yellow white solid.

Workup

  1. additionwas added
  2. temperatureAfter cooling
  3. customthe insoluble matter was separated by filtration through Celite
  4. customthe reaction solvent was evaporated away under reduced pressure
  5. dissolutionThe resulting residue was dissolved in ethyl acetate
  6. washwashed with water and saturated brine
  7. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  8. customthe solvent was evaporated away under reduced pressure
  9. washeluted wrath a mixed solvent of n-hexane/ethyl acetate (3:1
  10. customv/v) to obtain the entitled compound (20.12 g, quant) as a yellow white solid

Sources & evidence

ORD record
ord-712fca5e5a9043b1b1ed8c4e58a18591
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

Loading…