Diisopropylamine → ethyl 2-((2-chloro-6-fluorophenyl)ethynyl)-1-(4-fluorophenyl)-1H-imidazole-5-carboxylate

HRID 2368502Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:10]=[C:9]2I)=[CH:4][CH:3]=1.C(NC(C)C)(C)C.[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[C:34]#[CH:35]>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.[Cu]I.C1COCC1>[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[C:28]=1[C:34]#[C:35][C:9]1[N:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][N:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Ethyl 1-(4-fluorophenyl)-2-iodo-1H-imidazole-5-carboxylate (38) (847 mg, 2.35 mmol), PdCl2(PPh3)2 (82 mg, 0.12 mmol), copper (I) iodide (22 mg, 0.12 mmol), and THF (50 mL) were added to a pressure tube. Diisopropyl amine (6 mL) and 1-chloro-2-ethynyl-3-fluorobenzene (41) (400 mg, 2.59 mmol) were added to the pressure tube and the reaction was stirred at 50° C. overnight. The reaction was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (0-30% EtOAc in hexanes) to provide ethyl 2-((2-chloro-6-fluorophenyl)ethynyl)-1-(4-fluorophenyl)-1H-imidazole-5-carboxylate (42).

Workup

concentrationThe reaction was concentrated in vacuo
customthe residue was purified by flash column chromatography on silica gel (0-30% EtOAc in hexanes)

Sources & evidence

ORD record: ord-5f5f0047e0f04acea07800d2822823c4
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08703776B2

Reaction notes

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