Sodium Carbonate → 2-fluoro-4-(4-methoxyphenyl)benzonitrile

HRID 494855Notes

Reaction equation

HRID 494855 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:13]1[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[C:15]([F:21])[CH:14]=1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>C(O)C.C1C=CC=CC=1.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>[F:21][C:15]1[CH:14]=[C:13]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH:20]=[CH:19][C:16]=1[C:17]#[N:18]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 201262(4-Methoxyphenyl)boronic acidHCID 7360294-Bromo-2-fluorobenzonitrile

Product 1

HCID 27633572-fluoro-4-(4-methoxyphenyl)benzonitrileYield 92%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolvent

Procedure

A mixture of 4-methoxyphenylboronic acid (4.56 g, 30.0 mmol) in ethanol (20 mL) was added to a solution of 4-bromo-2-fluorobenzonitrile (5.00 g, 25.0 mmol) and tetrakis(triphenylphosphine)palladium (578 mg, 0.50 mmol) in benzene (50 mL). The resulting mixture was treated with a 2.0 M aqueous solution of Na2CO3 (25 mL, 50 mmol) and heated briefly at reflux, then at 65° C. overnight. The mixture was cooled to room temperature and treated with 6.0 M aqueous NaOH. The aqueous phase was separated and extracted with ether. First the original organic phase and then the ethereal wash were filtered through diatomaceous earth. The collection flask was changed and the solids remaining atop the diatomaceous earth were washed through with EtOAc. The ethereal wash was concentrated and refiltered as before. The combined EtOAc rinses were combined and concentrated to provide the title compound as a yellow powder (92% yield). 1HNMR (300 MHz, d6-DMSO) δ 3.82 (s, 3H), 7.07 (d, 2H), 7.72 (dd, 1H), 7.79 (d, 2H), 7.85 (dd, 1H), 7.95 (dd, 1H).

Workup

  1. temperatureheated briefly
  2. temperatureat reflux
  3. customat 65° C.
  4. customovernight
  5. customThe aqueous phase was separated
  6. extractionextracted with ether
  7. washFirst the original organic phase and then the ethereal wash
  8. filtrationwere filtered through diatomaceous earth
  9. washwere washed through with EtOAc
  10. washThe ethereal wash
  11. concentrationwas concentrated
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-b5d5dd3addf84c73a5b2bcf9ad7a8808
Source dataset
uspto-grants-2009_05
Patent number
US07538138B2

Reaction notes

Loading…