Nitrogen → 1-(4-Chloro-3',5'-difluoro-5-methyl-6-nitrobiphenyl-2-yl)ethanone

HRID 1192708Notes

Reaction equation

HRID 1192708 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[N+:18]([O-:20])=[O:19])(=O)=O.[F:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[C:28]([F:30])[CH:29]=1.N#N>C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+].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>[Cl:16][C:10]1[C:9]([CH3:17])=[C:8]([N+:18]([O-:20])=[O:19])[C:7]([C:26]2[CH:25]=[C:24]([F:23])[CH:29]=[C:28]([F:30])[CH:27]=2)=[C:12]([C:13](=[O:15])[CH3:14])[CH:11]=1

Participants

7

Reactant 3

HCID 947NitrogenHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 866561856-Acetyl-4-chloro-3-methyl-2-nitrophenyl trifluoromethanesulfonate

Product 1

HCID 866561871-(4-Chloro-3',5'-difluoro-5-methyl-6-nitrobiphenyl-2-yl)ethanoneYield 100.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A biphasic solution of 6-acetyl-4-chloro-3-methyl-2-nitrophenyl trifluoromethanesulfonate (9.56 g, 26.4 mmol) and (3,5-difluorophenyl)boronic acid (5.00 g, 31.7 mmol) in toluene (100 mL) and saturated NaHCO3 (80 mL) was bubbled with N2 to degas. Tetrakis(triphenylphosphine)palladium(0) (1.22 g, 1.06 mmol) was added. The reaction mixture was bubbled with N2 for an additional 5 minutes and then heated at 80° C. for 2 hrs. After cooling to room temperature, the mixture was diluted with ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting material was purified on silica gel column, eluting with ethyl acetate/hexane, 0-30%, to give the desired product (8.65 g, 100%). LCMS calculated for C15H11ClFF2NO3 (M+H)+: m/z=326.0; Found: 326.0.

Workup

  1. customto degas
  2. customThe reaction mixture was bubbled with N2 for an additional 5 minutes
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting material was purified on silica gel column
  12. washeluting with ethyl acetate/hexane, 0-30%

Sources & evidence

ORD record
ord-11e6ae5e930941839db7629251d582df
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

Loading…