Triethylamine → 5-Bromo-7-fluoro-1H-indole-2-propanoic acid

HRID 1512855Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[C:6](I)[C:5]([NH2:9])=[C:4]([F:10])[CH:3]=1.[C:11]([OH:17])(=[O:16])[CH2:12][CH2:13][C:14]#[CH:15].C(N(CC)CC)C>CN(C=O)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>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[C:4]([F:10])[CH:3]=1)[NH:9][C:14]([CH2:13][CH2:12][C:11]([OH:17])=[O:16])=[CH:15]2

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (4-bromo-2-fluoro-6-iodophenyl)amine (D159) (2 g), 4-pentynoic acid (0.62 g) and copper(I) iodide (0.60 g) in DMF (4 mL) stirred under nitrogen at room temperature was added bis(triphenylphosphine)palladium(II) chloride (0.222 g), then triethylamine (2.2 mL) was added in a portion. The reaction mixture was stirred at 80° C. in microwave reactor for 2 hrs. The solid in the mixture was filtered, the filtrate was diluted with EtOAc (30 mL), washed with brine (80 mL) and water (50 mL×2). The organic layer was dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford 3-(5-bromo-7-fluoro-1H-indol-2-yl)propanoic acid (D160) (700 mg) as a yellow solid. MS (ES): C11H9BrFNO2 requires 285; found 286.0 (M+H+). δH (CDCl3, 400 MHz): 2.75 (2H, t), 3.07 (2H, t), 5.45 (1H, s), 7.05 (1H, d), 7.41 (1H, s).

Workup

filtrationThe solid in the mixture was filtered
additionthe filtrate was diluted with EtOAc (30 mL)
washwashed with brine (80 mL) and water (50 mL×2)
dry with materialThe organic layer was dried over anhydrous sodium sulfate
concentrationThe dried solution was concentrated
customThe residue was purified by column chromatography

Sources & evidence

ORD record: ord-6a6f3d4cf79d4d92aa9be0a455178675
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217028B2

Reaction notes

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