Azobisisobutyronitrile → (1-acetyl-5-bromomethyl-2-trifluoromethyl-1H-indol-3-yl)-acetic acid ethyl ester

HRID 402901Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:23])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH3:15])[CH:13]=2)[N:8]([C:16](=[O:18])[CH3:17])[C:7]=1[C:19]([F:22])([F:21])[F:20])[CH3:2].CC(N=NC(C#N)(C)C)(C#N)C.[Br:36]N1C(=O)CCC1=O>ClC(Cl)(Cl)Cl>[CH2:1]([O:3][C:4](=[O:23])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([CH2:15][Br:36])[CH:13]=2)[N:8]([C:16](=[O:18])[CH3:17])[C:7]=1[C:19]([F:20])([F:21])[F:22])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (1-acetyl-5-methyl-2-trifluoromethyl-1H-indol-3-yl)-acetic acid ethyl ester (3.25 g, 9.94 mmol), AIBN (408 mg, 2.49 mmol) and N-bromosuccinimide (1.77 g, 9.94 mmol) in tetrachloromethane (50 mL) is heated to 80° C. for 2 h. After cooling to room temperature, the reaction mixture is filtered and the filtrate concentrated in vacuo. The crude product is purified by flash column chromatography (silica gel, cyclohexane/EtOAc 9:1) to afford the title compound as a yellow solid (2.44 g, 6.02 mmol, 61%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.88 (s, J=8.8 Hz, 1H), 7.64 (s, 1H), 7.50 (d, J=8.8 Hz, 1H), 4.62 (s, 2H), 4.18 (q, J=7.1 Hz, 2H), 3.93 (s, 2H), 2.76 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 423 (M(C16H1579BrF3NO3)+H2O)+.

Workup

temperatureAfter cooling to room temperature
filtrationthe reaction mixture is filtered
concentrationthe filtrate concentrated in vacuo
customThe crude product is purified by flash column chromatography (silica gel, cyclohexane/EtOAc 9:1)

Sources & evidence

ORD record: ord-e830b3f7ebf342c2a34be2a03056edce
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08742132B2

Reaction notes

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