Azobisisobutyronitrile → tert-butyl-5-(bromomethyl)-4-chloro-1H-indole-1-carboxylate

HRID 475302Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([Cl:18])[C:13]([CH3:17])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:26])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([Cl:18])[C:13]([CH2:17][Br:26])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a stirred solution of 314 (38.1 g, 0.143 mol) in CCl4 (300 mL) at 80° C. was added NBS (30.6 g, 0.172 mol) followed by AIBN (1.2 g, 7.31 mmol), and the reaction mixture was stirred at 80° C. overnight. The cooled reaction mixture was diluted with EtOAc, and the organic layer was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (2 to 20% EtOAc) to afford 16.1 g (33%) of tert-butyl-5-(bromomethyl)-4-chloro-1H-indole-1-carboxylate (316) as a white solid: NMR (400 MHz, CDCl3) δ 8.03 (d, J=8.4 Hz, 1H), 7.63 (s, 1H), 7.36 (d, J=8.4 Hz, 1H), 6.71 (d, J=3.8 Hz, 1H), 4.75 (s, 2H), 1.67 (s, 9H).

Workup

customThe cooled reaction mixture
washthe organic layer was washed with water and brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by SiO2 chromatography
washeluting with an EtOAc/hexane gradient (2 to 20% EtOAc)

Sources & evidence

ORD record: ord-1286a28efa5d49fea633825d8b670d0a
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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