Nitrogen → 6-Acetyl-4-chloro-3',5'-difluoro-3-methylbiphenyl-2-carbonitrile

HRID 1499722Notes

Reaction equation

HRID 1499722 reaction equation
FC(F)(F)S(O[C:7]1[C:12]([C:13](=[O:15])[CH3:14])=[CH:11][C:10]([Cl:16])=[C:9]([CH3:17])[C:8]=1[C:18]#[N:19])(=O)=O.[F:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[C:27]([F:29])[CH:28]=1.C(=O)([O-])O.[Na+].N#N>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>[C:13]([C:12]1[CH:11]=[C:10]([Cl:16])[C:9]([CH3:17])=[C:8]([C:18]#[N:19])[C:7]=1[C:25]1[CH:24]=[C:23]([F:22])[CH:28]=[C:27]([F:29])[CH:26]=1)(=[O:15])[CH3:14]

Participants

8

Reactant 4

HCID 947NitrogenHCID 516892Sodium Bicarbonate2×HCID 2734338(3,5-Difluorophenyl)boronic acidHCID 583686446-Acetyl-4-chloro-2-cyano-3-methylphenyl trifluoromethanesulfonate

Product 1

HCID 866667936-Acetyl-4-chloro-3',5'-difluoro-3-methylbiphenyl-2-carbonitrileYield 99%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A biphasic solution of 6-acetyl-4-chloro-2-cyano-3-methylphenyl trifluoromethanesulfonate (3.07 g, 8.98 mmol) and (3,5-difluorophenyl)boronic acid (1.70 g, 10.8 mmol) in toluene (30 mL)/0.8 M sodium hydrogencarbonate in water (30 mL, 30 mmol) (this was saturated NaHCO3 in water) was degassed with N2. Tetrakis(triphenylphosphine)palladium(0) (0.414 g, 0.359 mmol) was added. The mixture was degassed with N2 for 5 min. and heated at 80° C. for 2 h. After cool to rt, the mixture was diluted with EtOAc. The layers were separated and the aq. layer was extracted with more EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to crude, dark solid. The material was dissolved in CHCl3 and purified on silica gel column, eluting with 0 to 20% of EtOAc in hexanes, to give the desired product (2.71 g, 99%). LCMS calculated for C16H11ClF2NO (M+H)+: m/z=306.0; Found: 306.1.

Workup

  1. customThe mixture was degassed with N2 for 5 min.
  2. temperatureAfter cool to rt
  3. additionthe mixture was diluted with EtOAc
  4. customThe layers were separated
  5. extractionthe aq. layer was extracted with more EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to crude, dark solid
  10. dissolutionThe material was dissolved in CHCl3
  11. custompurified on silica gel column
  12. washeluting with 0 to 20% of EtOAc in hexanes

Sources & evidence

ORD record
ord-2c9af7948be8446bbf870f5e56b0d104
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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