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1-Fluoro-2-iodo-4-(methylsulfonyl)benzene → Tert-butyl(4-cyano-2-{[2-fluoro-5-(methylsulfonyl)phenyl]ethynyl}phenoxy)acetate

HRID 2390166
Notes
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Reaction equation

HRID 2390166 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[C:17]#[CH:18])([CH3:4])([CH3:3])[CH3:2].[F:20][C:21]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][C:22]=1I>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].C1COCC1>[C:1]([O:5][C:6](=[O:19])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][C:10]=1[C:17]#[C:18][C:22]1[CH:23]=[C:24]([S:27]([CH3:30])(=[O:28])=[O:29])[CH:25]=[CH:26][C:21]=1[F:20])([CH3:4])([CH3:3])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 585218581-Fluoro-2-iodo-4-(methylsulfonyl)benzene2×HCID 58522073Tert-butyl(4-cyano-2-ethynylphenoxy)acetate2×

Product 1

HCID 58521827Tert-butyl(4-cyano-2-{[2-fluoro-5-(methylsulfonyl)phenyl]ethynyl}phenoxy)acetateYield 78%

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Catalyst
HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of (4-cyano-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 46; 200 mg; 0.78 mmol), 1-fluoro-2-iodo-4-(methylsulfonyl)benzene (Intermediate 77; 233 mg; 0.78 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) (34 mg; 0.05 mmol) and cuprous iodide (9 mg; 0.05 mmol) was degassed during 2 minutes under nitrogen then anhydrous THF (3 ml) and TEA (215 μl; 1.55 mmol) were added and the reaction mixture was stirred at 70° C. for 16 hours. The solvents were removed under reduced pressure and the residue was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc to give the title compound (260 mg, 78%) as a yellow sticky solid.

Workup

  1. customwas degassed during 2 minutes under nitrogen
  2. customThe solvents were removed under reduced pressure
  3. customthe residue was purified by flash column chromatography (silica)
  4. washeluting with cyclohexane containing
  5. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-aef323e15f7d4082a9a9aaa18fcadc05
Source dataset
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08273769B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes