Triethylamine → 2-Cyclopropylethynyl-4-fluoro-phenylamine

HRID 2382129Notes

Reaction equation

HRID 2382129 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4](I)[CH:3]=1.[CH:10]1([C:13]#[CH:14])[CH2:12][CH2:11]1.C(N(CC)CC)C>C1COCC1.[Cu]I>[CH:10]1([C:13]#[C:14][NH:6][C:5]2[CH:7]=[CH:8][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:12][CH2:11]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 138823CyclopropylacetyleneHCID 27782834-Fluoro-2-iodoaniline

Product 1

HCID 685573712-Cyclopropylethynyl-4-fluoro-phenylamineYield 74.7%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-fluoro-2-iodoaniline (2 g, 8.4 mmol) in THF (15 mL) and cyclopropylacetylene (1.4 mL, 16.9 mmol) is treated with PdCl2(PPh3)4 (177 mg, 0.25 mmol), CuI (48 mg, 0.25 mmol) and triethylamine (3.5 mL, 25.2 mmol) and stirred at rt for 2 h. The mixture is filtered through Celite and concentrated. The residue is purified by silica gel chromatography eluting with 0%-35% EtOAc in heptane to afford 2-cyclopropylethynyl-4-fluoro-phenylamine (1.1 g, 74%). MS: 176 (M+H); 1H NMR (300 MHz, CDCl3): δ 6.93 (m, 1H), 6.81 (m, 1H), 6.59 (m, 1H), 4.00 (s, NH2, 2H), 1.49 (m, 1H), 0.82 (m, 4H).

Workup

  1. filtrationThe mixture is filtered through Celite
  2. concentrationconcentrated
  3. customThe residue is purified by silica gel chromatography
  4. washeluting with 0%-35% EtOAc in heptane

Sources & evidence

ORD record
ord-7e6b5b5616144dbca57eea1085e34fff
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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