4-Bromo-2-fluorobenzonitrile → HCID 12991232, compound

HRID 48365Notes

Reaction equation

HRID 48365 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][CH:12]=[CH2:13])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C12CCCC(CCC1)B12[H]B2(C3CCCC2CCC3)[H]1.Br[C:35]1[CH:42]=[CH:41][C:38]([C:39]#[N:40])=[C:37]([F:43])[CH:36]=1>C1COCC1.Cl[Pd]Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:39]([C:38]1[CH:41]=[CH:42][C:35]([CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:10])=[CH:36][C:37]=1[F:43])#[N:40]

Participants

6

Reactant 2

HCID 7360294-Bromo-2-fluorobenzonitrileHCID 10931982benzyl N-ethenylcarbamate

Product 1

HCID 12991232HCID 12991232, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-10 °C

Procedure

Into a 100 mL single neck flask was placed (phenylmethoxy)-N-vinylcarboxamide (5.54 g, 31.25 mmol) in THF (15 mL). The mixture was cooled down to −10° C. while treated dropwise with a solution of 9-BBN dimer (3.81 g, 15.62 mmol) in THF (20 mL). The reaction mixture was warmed up to RT while stirring for additional 2 hours. The reaction mixture was quenched with 3N NaOH (2mL) and the mixture was stirred for 10 minutes before its addition to a solution of 4-bromo-2-fluorobenzonitrile (5 g, 25 mmol) and [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (II), PdCl2(dppf), (0.4 g, 0.5 mmol) in THF (10 mL). The mixture was stirred at RT for 12 hour and then was quenched with a 2:1 mixture of pH=7 buffer hydrogen peroxide (10 mL). The product was extracted with EtOAc and the organic layer was separated and washed twice with H2O, dried over anhydrous Na2SO4, filtered, and concentrated under reduced vacuum. The resulting semi-solid was further purified via flash chromatography (Silica gel, isocratic) and eluting with a solvent of Hexanes/EtOAc 50% to provide the intermediate title compound, N-[2-(4-cyano-3-fluorophenyl)ethyl](phenylmethoxy)carboxamide, (6.4 g, 86%) as a white solid. Electron spray M.S. 299 (M*+H).

Workup

  1. customInto a 100 mL single neck flask was placed
  2. temperatureThe reaction mixture was warmed up to RT
  3. customThe reaction mixture was quenched with 3N NaOH (2mL)
  4. stirringThe mixture was stirred at RT for 12 hour
  5. customwas quenched with a 2:1 mixture of pH=7 buffer hydrogen peroxide (10 mL)
  6. extractionThe product was extracted with EtOAc
  7. customthe organic layer was separated
  8. washwashed twice with H2O
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced vacuum
  12. customThe resulting semi-solid was further purified via flash chromatography (Silica gel, isocratic)
  13. washeluting with a solvent of Hexanes/EtOAc 50%

Sources & evidence

ORD record
ord-6409241db45a4199b526eae032053211
Source dataset
uspto-grants-2004_03
Patent number
US06703425B2

Reaction notes

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