Hexane → 5-Chloro-3-(2,4-dimethoxypyrimidin-5-yl)-3-hydroxy-1,3-dihydroindol-2-one

HRID 601759

Reaction equation

C([Li])CCC.CCCCCC.Br[C:13]1[C:14]([O:21][CH3:22])=[N:15][C:16]([O:19][CH3:20])=[N:17][CH:18]=1.[Cl:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28](=[O:33])[C:27]2=[O:34].[Cl-].[NH4+]>C1COCC1>[Cl:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28](=[O:33])[C:27]2([C:13]1[C:14]([O:21][CH3:22])=[N:15][C:16]([O:19][CH3:20])=[N:17][CH:18]=1)[OH:34]

Participants

Conditions

Temperature: -78 °C

Procedure

A 1.6 M solution of n-butyllithium in hexane (10 ml, 16 mmol) was added dropwise to a solution of 5-bromo-2,4-dimethoxypyrimidine (3.29 g, 15 mmol) in THF (50 ml) at −78° C. After stirring at −78° C. for 0.5 h, a suspension of 5-chloroisatin (1.27 g, 7.0 mmol) in THF (50 ml) was added dropwise. The reaction mixture was allowed to warm to room temperature and then saturated ammonium chloride solution was added. The mixture was extracted three times with ethyl acetate, and the combined organic layers were washed with saturated brine. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by chromatography (silica gel, 50% ethyl acetate in dichloromethane) resulted in 0.97 g of the intermediate.

Workup

additionwas added dropwise
temperatureto warm to room temperature
extractionThe mixture was extracted three times with ethyl acetate
washthe combined organic layers were washed with saturated brine
dry with materialThe organic phase was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification by chromatography (silica gel, 50% ethyl acetate in dichloromethane)

Sources & evidence

ORD record: ord-7adaf7ffb7214d29a178fe10515f228e
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07902379B2

Linked notes

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