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

HRID 2040422Notes

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-0889878449df454a951ae9b263bb99c4
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580842B2

Reaction notes

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