Sodium hydride → 6-Bromo-1-(2-methoxy-ethyl)-1H-indole-3-carboxylic acid methyl ester

HRID 250231Notes

Reaction equation

[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([Br:16])=[CH:13][CH:14]=2)[NH:9][CH:8]=1)=[O:6].Br[CH2:18][CH2:19][O:20][CH3:21]>CN(C=O)C>[CH3:3][O:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][C:12]([Br:16])=[CH:13][CH:14]=2)[N:9]([CH2:18][CH2:19][O:20][CH3:21])[CH:8]=1)=[O:6]

Participants

Conditions

Temperature: 60 °C

Procedure

Sodium hydride (60% in mineral oil, 87 mg, 2.2 mmol) is added to a solution of 6-bromo-1H-indole-3-carboxylic acid methyl ester (500 mg, 1.97 mmol) in DMF (5 mL) at room temperature and the mixture is stirred for 30 minutes. To the reaction mixture is added 1-bromo-2-methoxy-ethane (222 μL, 2.36 mmol). After one hour, sodium hydride (20 mg) is added. Thirty minutes later, 1-bromo-2-methoxy-ethane (60 μL) is added. The mixture is heated to 60° C. for one hour. The cooled mixture is quenched with a small amount of water and concentrated under reduced pressure. The residue is taken up in ethyl acetate and filtered. The filtrate is concentrated under reduced pressure and the resulting residue is purified by column chromatography (gradient: 10 to 60% ethyl acetate/heptane) followed by purification via radial chromatography (gradient: 0 to 1% MeOH/CH2Cl2) to provide the title compound (386 mg, 63%). ES/MS m/e 314.0 (M+2).

Workup

waitAfter one hour
customThe cooled mixture is quenched with a small amount of water
concentrationconcentrated under reduced pressure
filtrationfiltered
concentrationThe filtrate is concentrated under reduced pressure
customthe resulting residue is purified by column chromatography (gradient: 10 to 60% ethyl acetate/heptane)
customfollowed by purification via radial chromatography (gradient: 0 to 1% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-f3dfac47506d48e78a855f4799b568e0
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863302B2

Reaction notes

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