Benzoyl Peroxide → 2-Bromomethyl-1-tert-butoxycarbonyl-5-chloroindole

HRID 1432873Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A solution containing 5-chloro-2-methyl-indole-1-carboxylic acid tert-butyl ester (3.0 g, 11.3 mmol), NBS (1.33 g, 11.3 mmol), and benzoyl peroxide (0.4 g, 1.13 mmol) in CCl4 (100 mL) is heated at 80° C. for 3 hours. An additional portion of NBS (0.65 g, 5.65 mmol), and benzoyl peroxide (0.2 g, 0.56 mmol) is then added and the reaction mixture is heated for an additional 3 hours. After cooling to ambient temperature, the reaction mixture is filtered. The filtrate is concentrated to a brown oil which is triturated with hexane to remove residual succinimide, filtered, and concentrated. The resultant oil (4.5 g, >100%) is used directly in the next reaction without further purification. 1H NMR (300 MHz, CDCl3) δ1.72 (s, 9H), 4.88 (s, 2H), 6.63 (s, 1H), 7.27 (dd, J=9.0, 2.0 Hz, 1H), 7.46 (d, J=2.0 Hz, 1H), 8.09 (d, J=9.0 Hz, 1H) ppm; MS (EI): m/z 343 (M+).

Workup

temperaturethe reaction mixture is heated for an additional 3 hours
temperatureAfter cooling to ambient temperature
filtrationthe reaction mixture is filtered
concentrationThe filtrate is concentrated to a brown oil which
customis triturated with hexane
customto remove residual succinimide
filtrationfiltered
concentrationconcentrated
customThe resultant oil (4.5 g, >100%) is used directly in the next reaction without further purification

Sources & evidence

ORD record: ord-732c288384e644a2bd2c65e1d83e49f3
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612075B2

Reaction notes

Loading…