tert-butyl-5-(bromomethyl)-4-chloro-1H-indole-1-carboxylate → tert-butyl-4-chloro-5-((1,3-dioxoisoindolin-2-yl)methyl)-1H-indole-1-carboxylate

HRID 475303Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([Cl:19])[C:13]([CH2:17]Br)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:20]1(=[O:30])[NH:24][C:23](=[O:25])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12.[K]>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([Cl:19])[C:13]([CH2:17][N:24]3[C:20](=[O:30])[C:21]4[C:22](=[CH:26][CH:27]=[CH:28][CH:29]=4)[C:23]3=[O:25])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 316 (16.1 g, 0.0467 mol) and potassium phthalimide (26.1 g, 0.141 mol) in anhydrous DMF (150 mL) 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 (5 to 20% EtOAc) to afford 10.8 g (56%) of tert-butyl-4-chloro-5-((1,3-dioxoisoindolin-2-yl)methyl)-1H-indole-1-carboxylate (318) as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J=8.2 Hz, 1H), 7.88-7.86 (m, 2H), 7.74-7.72 (m, 2H), 7.62 (d, J=3.7 Hz, 1H), 7.27-7.25 (m, 2H), 5.12 (s, 2H), 1.65 (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 (5 to 20% EtOAc)

Sources & evidence

ORD record: ord-9c8e3514816d4179b6e1262ffdc3c547
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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