Trimethylsilylacetylene → 2-Fluoro-4-((trimethylsilyl)ethynyl)aniline

HRID 2181426Notes

Reaction equation

HRID 2181426 reaction equation
[F:1][C:2]1[CH:8]=[C:7](I)[CH:6]=[CH:5][C:3]=1[NH2:4].[Si:10]([C:14]#[CH:15])([CH3:13])([CH3:12])[CH3:11]>C(OCC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:8]=[C:7]([C:15]#[C:14][Si:10]([CH3:13])([CH3:12])[CH3:11])[CH:6]=[CH:5][C:3]=1[NH2:4]

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 1856942-Fluoro-4-iodoaniline

Product 1

HCID 220256802-Fluoro-4-((trimethylsilyl)ethynyl)aniline

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

2-Fluoro-4-iodoaniline (5.00 g, 21.1 mmol), CuI (90 mg, 0.42 mmol), and (Ph3P)2PdCl2 (300 mg, 0.42 mmol) were weighed into a flask which was sealed and flushed with N2. A solution of TMS-acetylene (2.28 g, 23.2 mmol) in TEA (20 mL) was added, then the entire mixture stirred 15 hours at room temperature. The reaction mixture was diluted with diethyl ether (200 mL), filtered through Celite®, then all solvents removed under reduced pressure. The resulting dark brown oil was purified by filtration through a plug of flash silica (5% EtOAc/hexanes as eluant) to afford the desired product as a pale brown oil which rapidly solidified to give a crystalline solid (3.85 g, 88%); m.p. (EtOAc/hexanes) 45-47° C. 1H NMR (400 MHz, CDCl3) δ 7.10 (dd, J=11.7, 1.8 Hz, 1 H), 7.06 (ddd, J=8.3, 1.8, 1.0 Hz, 1 H), 6.66 (dd, J=9.4, 8.3 Hz, 1 H), 3.86 (br s, 2 H), 0.22 (s, 9 H). Anal. Calcd for C11H14FNSi: C, 63.7; H, 6.8; N, 6.8. Found: C, 63.7; H, 6.9; N, 6.7. Step B: Preparation of 3,4-difluoro-2-[[2-fluoro-4(trimethylsilylethynyl)phenyl]amino]benzoic acid

Workup

  1. customwhich was sealed
  2. customflushed with N2
  3. filtrationfiltered through Celite®
  4. customall solvents removed under reduced pressure
  5. filtrationThe resulting dark brown oil was purified by filtration through a plug of flash silica (5% EtOAc/hexanes as eluant)

Sources & evidence

ORD record
ord-15fe4e1a32a942b88d01956f6f6814ea
Source dataset
uspto-grants-2005_05
Patent number
US06891066B2

Reaction notes

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