Sodium hydride → tert-Butyl (5-bromo-1-oxo-1,3-dihydro-2H-isoindol-2-yl)acetate

HRID 521186Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][CH2:5]2.[H-].[Na+].Br[CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C([O-])(O)=O.[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:5]2

Participants

Conditions

Temperature: 0 °C

Procedure

5-Bromo-2,3-dihydro-1H-isoindol-1-one (100 mg, 0.47 mmol) was dissolved in DMF (4.7 mL) and stirred at 0° C. NaH (38 mg, 0.94 mmol, 60% dispersion in oil) was carefully added in two portions, and the resulting mixture was allowed to stir at 0° C. for 15 minutes before tert-butyl bromoacetate (92 mg, 0.47 mmol) was added. The mixture was allowed to stir at 0° C. for 30 minutes before saturated aqueous NaHCO3 (10 mL) was carefully added. The mixture was extracted with EtOAc, and the organic layer was washed with water, brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-20% EtOAc/hexanes). Desired fractions were identified, combined, and concentrated in vacuo to afford the title compound. LRMS (ESI) calc'd for C14H16BrNO3 [M+Na]+: 348. Found: 348.

Workup

additionwas added
additionwas carefully added
extractionThe mixture was extracted with EtOAc
washthe organic layer was washed with water, brine
dry with materialdried over anhydrous MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by MPLC on silica gel (
washa gradient elution of 0-20% EtOAc/hexanes)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-a549963f323f4d8186a298dc7a01065f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328099B2

Reaction notes

Loading…