Diethyl Ether → 1-ethyl-2-(3-hydroxy-phenyl)-6-methoxy-1H-indole-3-carbonitrile

HRID 1009530Notes

Reaction equation

[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]#[N:15])=[C:4]1[Sn](CCCC)(CCCC)CCCC)[CH3:2].I[C:30]1[CH:31]=[C:32]([OH:36])[CH:33]=[CH:34][CH:35]=1.C1COCC1.CCOCC>CCOC(C)=O.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.[Cu]I>[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[C:5]([C:14]#[N:15])=[C:4]1[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=1)[CH3:2]

Participants

Conditions

Temperature: 65 °C

Procedure

1-Ethyl-6-methoxy-2-tributylstannanyl-1H-indole-3-carbonitrile (1.0 g, 2.05 mmol), prepared in step A, is combined with 3-iodophenol (474 mg, 2.15 mmol), Pd(PPh3)2Cl2 (67 mg, 0.102 mmol), CuI (75 mg, 0.39 mmol) and THF (4.0 mL). This mixture is heated at 65° C. overnight. The reaction mixture is diluted in EtOAc, and is filtered through celite. The filtrate is concentrated and the residue is purified by silica gel chromatography (4:1, CH2Cl2/EtOAc) to yield crude product. Ether trituration yields 1-ethyl-2-(3-hydroxy-phenyl)-6-methoxy-1H-indole-3-carbonitrile (430 mg, 72%) as a yellow-white solid.

Workup

filtrationis filtered through celite
concentrationThe filtrate is concentrated
customthe residue is purified by silica gel chromatography (4:1, CH2Cl2/EtOAc)
customto yield crude product

Sources & evidence

ORD record: ord-b628d4b61d91433ba37e98d05991e051
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07973069B2

Reaction notes

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