Potassium Carbonate → [5-(4-Fluoro-phenoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetic acid methyl ester

HRID 523698Notes

Reaction equation

HRID 523698 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[C:12](=[O:16])[NH:11][C:10]3=[O:17])=[CH:4][CH:3]=1.[CH3:20][O:21][C:22](=[O:25])[CH2:23]Br.C([O-])([O-])=O.[K+].[K+]>>[CH3:20][O:21][C:22](=[O:25])[CH2:23][N:11]1[C:10](=[O:17])[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([O:6][C:5]3[CH:18]=[CH:19][C:2]([F:1])=[CH:3][CH:4]=3)[CH:8]=2)[C:12]1=[O:16]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 60984Methyl bromoacetateHCID 667126295-(4-Fluoro-phenoxy)-isoindole-1,3-dione

Product 1

HCID 66713045[5-(4-Fluoro-phenoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetic acid methyl esterYield 90.4%

Procedure

A mixture of 5-(4-fluoro-phenoxy)-isoindole-1,3-dione (42.9 g, 167 mmol), Bromo-acetic acid methyl ester (21.1 ml, 223 mmol), K2CO3 (62.3 g, 446 mmol) and Et2CO (700 ml) was refluxed with stirring for 16 h before the mixture was concentrated in vacuo. To the residue was added water (150 ml) and the resulting slurry was extracted with EtOAc (1×750 ml, 1×250 ml). The combined organic phases were dried over MgSO4 and concentrated in vacuo to give the title compound as a tan solid (49.7 g); 1H NMR (CDCl3) δ=7.80 (d, 1H), 7.01 to 7.30 (m, 6H), 4.41 (s, 2H), 3.76 (s, 3H).

Workup

  1. temperaturewas refluxed
  2. concentrationwas concentrated in vacuo
  3. additionTo the residue was added water (150 ml)
  4. extractionthe resulting slurry was extracted with EtOAc (1×750 ml, 1×250 ml)
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-38484d2b300542ba97ad1fbabcbc70c3
Source dataset
uspto-grants-2016_05
Patent number
US09339527B2

Reaction notes

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