Water → tert-butyl 2-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1-carboxylate

HRID 521808Notes

Reaction equation

[C:1]([N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1B(O)O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[C:17]1[CH:22]=[C:21]([O:23][C:24]2[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=2)[CH:20]=[CH:19][N:18]=1.C([O-])([O-])=O.[Na+].[Na+].O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:28][C:27]1[CH:29]=[CH:30][C:24]([O:23][C:21]2[CH:22]=[CH:17][N:18]=[C:19]([C:9]3[N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH:12]=[CH:11][CH:10]=3)[CH:20]=2)=[CH:25][CH:26]=1

Participants

Conditions

Temperature: 72 °C

Procedure

To a stirred mixture of N-Boc-pyrrole-2-boronic acid (114 mg, 0.54 mmol) and 4-((2-chloropyridin-4-yl)oxy)aniline (100 mg, 0.45 mmol) in 8 ml of 1,4-dioxane, was added PdCl2(PPh3)2 (10 mg, 0.014 mmol) and 1M Na2CO3 aqueous solution (0.5 ml, 1.0 mmol). The mixture was heated at 72° C. under N2 for one hour, cooled to room temperature and poured into 100 ml of water. The resulting mixture was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (50 ml), dried over Na2SO4, and evaporated to give a brown oil, which was purified by silica gel chromatography with a gradient of 20˜50% EtOAc/hexanes to give tert-butyl 2-[4-(4-aminophenoxy)pyridin-2-yl]-1H-pyrrole-1-carboxylate as colorless oil. Yield: 110 mg, 70%.

Workup

temperaturecooled to room temperature
extractionThe resulting mixture was extracted with EtOAc (2×50 ml)
washwashed with brine (50 ml)
dry with materialdried over Na2SO4
customevaporated
customto give a brown oil, which
customwas purified by silica gel chromatography with a gradient of 20˜50% EtOAc/hexanes

Sources & evidence

ORD record: ord-5d29d068c50e408fade6dd759e67e00e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328103B2

Reaction notes

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