Sodium Carbonate → 2-(6-Bromo-5-methylpyridin-2-yl)isoindoline-1,3-dione

HRID 1505053Notes

Reaction equation

[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][N+:13]=1[O-].P(Br)(Br)([Br:22])=O.C([O-])([O-])=O.[Na+].[Na+]>ClC(Cl)C>[Br:22][C:14]1[N:13]=[C:12]([N:3]2[C:2](=[O:1])[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4]2=[O:11])[CH:17]=[CH:16][C:15]=1[CH3:18]

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of 2-(1,3-dioxoisoindolin-2-yl)-5-methylpyridine 1-oxide (501 mg, 1.97 mmol) in 1,1-dichloroethane (5 ml) is added POBr3 (679 mg, 2.36 mmol) in small portions at 0° C., and the solution is then heated at 40° C. for 2 hours. The solution is cooled to room temperature, poured into crushed ice, neutralized with Na2CO3 and extracted with dichloromethane. The separated organic layer is further washed with water, brine and dried over Na2SO4. After concentration, the crude product is purified by silica gel flash chromatography, eluted with 3% ethyl acetate in dichloromethane to afford 2-(6-bromo-5-methylpyridin-2-yl)isoindoline-1,3-dione as an off-white solid. LC-MS m/z: 317.2 (M+1).

Workup

temperatureThe solution is cooled to room temperature
additionpoured
custominto crushed ice
extractionextracted with dichloromethane
washThe separated organic layer is further washed with water, brine
dry with materialdried over Na2SO4
concentrationAfter concentration
customthe crude product is purified by silica gel flash chromatography
washeluted with 3% ethyl acetate in dichloromethane

Sources & evidence

ORD record: ord-aad7906a5766429b93f47f9420f4018e
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216964B2

Reaction notes

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