Nitrogen → 6-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-carbonitrile

HRID 1192588Notes

Reaction equation

HRID 1192588 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]=[CH:27][CH:28]=1.O.N#N>C1(C)C=CC=CC=1.[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>[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:27]1[CH:26]=[CH:25][CH:24]=[C:23]([F:22])[CH:28]=1)(=[O:15])[CH3:14]

Participants

8

Reactant 4

HCID 947NitrogenHCID 962WaterHCID 27339863-Fluorophenylboronic acidHCID 583686446-Acetyl-4-chloro-2-cyano-3-methylphenyl trifluoromethanesulfonate

Product 1

HCID 583684696-Acetyl-4-chloro-3'-fluoro-3-methylbiphenyl-2-carbonitrileYield 99%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 5360545SodiumSolvent

Conditions

Temperature
80 °C

Procedure

A biphasic solution of 6-acetyl-4-chloro-2-cyano-3-methylphenyl trifluoromethanesulfonate (2.537 g, 7.425 mmol) and (3-fluorophenyl)boronic acid (1.56 g, 11.1 mmol) in toluene (70 mL) and 0.8 M sodium hydrogenecarbonate in water (70 mL, 50 mmol) was bubbled with N2 to degas. Tetrakis(triphenylphosphine)palladium(0) (0.429 g, 0.371 mmol) was added. The mixture was degassed with N2 for an additional 5 minutes and then heated at 80° C. for 2 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate. The layers were separated and the aq. layer was extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to a dark solid. The material was dissolved in CHCl3 and was purified on silica gel column, eluting with 0 to 40% ethyl acetate in hexane, to give the desired product (2.105 g, 99%). LCMS calculated for C16H12ClFNO (M+H)+: m/z=288.1; Found: 288.1.

Workup

  1. customto degas
  2. customThe mixture was degassed 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 aq. layer was extracted with ethyl acetate
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to a dark solid
  11. dissolutionThe material was dissolved in CHCl3
  12. customwas purified on silica gel column
  13. washeluting with 0 to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-ba713af4df3e4da482ee9891e20427fb
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

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