3,5-Dibromopyridine → 2-(5-Bromo-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester

HRID 712603Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1B(O)O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:20][C:21]1[CH:22]=[N:23][CH:24]=[C:25](Br)[CH:26]=1.CC([O-])=O.[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:25]1[CH:24]=[N:23][CH:22]=[C:21]([Br:20])[CH:26]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

1-(tert-Butoxycarbonyl)indole-2-boronic acid (900 mg, 3.5 mmol), 3,5-dibromo-pyridine (810 mg, 3.5 mmol), KOAc (1.01 g, 10.4 mmol) and Pd(dppf)Cl2 (252 mg, 0.35 mmol) are mixed in 1,4-dioxane (70 mL) and heated to 80° C. for 2 hours. The mixture is filtered and the filtrate is concentrated. The residue is dissolved in DCM and washed with water. The organic layer is separated, dried over Na2SO4, filtered and concentrated to afford the crude product which is purified by column chromatography to give 320 mg of 2-(5-bromo-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester.

Workup

filtrationThe mixture is filtered
concentrationthe filtrate is concentrated
dissolutionThe residue is dissolved in DCM
washwashed with water
customThe organic layer is separated
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto afford the crude product which
customis purified by column chromatography

Sources & evidence

ORD record: ord-8ff11408cbda479188f4a9423fed6c83
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181272B2

Reaction notes

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