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Ethyl Acetate → 2-Fluoro-3-methoxy-4-nitrobenzonitrile

HRID 914202
Notes
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Reaction equation

HRID 914202 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[C:3]=1[F:13].[CH3:14][N:15](C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.C(OCC)(=O)C>CC(N(C)C)=O.[Pd].[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:13][C:3]1[C:4]([O:11][CH3:12])=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:14]#[N:15]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 3

HCID 8857Ethyl AcetateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 579555891-Bromo-2-fluoro-3-methoxy-4-nitrobenzene

Product 1

HCID 579555492-Fluoro-3-methoxy-4-nitrobenzonitrileYield 433.4%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst
HCID 23938PalladiumCatalyst
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-Bromo-2-fluoro-3-methoxy-4-nitrobenzene (250 mg, 1 mmol) and zinc cyanide (70 mg, 0.6 mmol) were stirred in DMA (5 mL) and purged with nitrogen. The palladium catalyst, Pd2(dba)3 (92 mg, 0.1 mmol), and the ligand, Davephos (79 mg, 0.2 mmol), were added and the reaction mixture was stirred at 90° C. overnight. It was then cooled to rt., diluted to ethyl acetate, washed with brine. Organic dried, concentrated and purified by flash column (EtOAc/Hexane=1:20) to give 170 mg product (87%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 4.15 (s, 3H) 7.42 (dd, J=9.0, 6.2 Hz, 1H) 7.65 (dd, J=9.0, 1.9 Hz, 1H).

Workup

  1. custompurged with nitrogen
  2. temperatureIt was then cooled to rt
  3. washwashed with brine
  4. concentrationOrganic dried, concentrated
  5. custompurified by flash column (EtOAc/Hexane=1:20)

Sources & evidence

ORD record
ord-ecf7fdda55034b4fafd34377b486264c
Source dataset
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08026234B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes