Iodine → 1-ethyl-2-iodo-6-methoxy-1H-indole-3-carbonitrile

HRID 252488Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[CH2:9]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([C:22]#[N:23])=[CH:12]1)[CH3:10].[I:24]I>C1COCC1>[CH2:9]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([C:22]#[N:23])=[C:12]1[I:24])[CH3:10]

Participants

Conditions

Temperature: -30 °C

Procedure

A 2M solution of lithium diisopropyl amide in THF/hexanes (Acros) (3.9 mL, 7.8 mmol) is diluted with THF (5 mL) in a flame-dried flask. After cooling the reaction to −30° C., a solution of 1-ethyl-6-methoxy-1H-indole-3-carbonitrile (1.30 g, 6.5 mmol) in THF (10 mL) is added dropwise during 10 min, maintaining the temperature at −30° C. After stirring for an additional 30 min at this temperature, a solution of iodine (2.31 g, 9.1 mmol) in THF (5 mL) is added during 10 min. After the addition, the reaction is warmed to ambient temperature during 1 h. The reaction is then diluted with ice-H2O and extracted with EtOAc (2×). The combined organic phases are washed with 1M sodium thiosulfate and saturated NaCl and then concentrated to a brown solid. Chromatography (CH2Cl2/hexanes, 1/1) over silica gel gives 1.31 g (62%) of 1-ethyl-2-iodo-6-methoxy-1H-indole-3-carbonitrile as an off-white solid.

Workup

temperatureAfter cooling
customthe reaction to −30° C.
additionAfter the addition
temperaturethe reaction is warmed to ambient temperature during 1 h
extractionextracted with EtOAc (2×)
washThe combined organic phases are washed with 1M sodium thiosulfate and saturated NaCl
concentrationconcentrated to a brown solid

Sources & evidence

ORD record: ord-bac93d07f5c8491aa0047354110b9583
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868037B2

Reaction notes

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