Sodium hydride → 5-Fluoro-1-(4-methoxybenzyl)indoline-2,3-dione

HRID 15266

Reaction equation

HRID 15266 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].[H-].[Na+].[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Cl)=[CH:19][CH:18]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:21][C:20]1[CH:23]=[CH:24][C:17]([O:16][CH3:15])=[CH:18][CH:19]=1)[C:6](=[O:11])[C:5]2=[O:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 2365665-Fluoroisatin

Product 1

HCID 76771005-Fluoro-1-(4-methoxybenzyl)indoline-2,3-dioneYield 82.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-fluoroisatin (5 g, 30.2 mmol) in DMF (60 mL) was cooled in an ice/water bath and treated with sodium hydride (1.44 g, 60.6 mmol) portionwise. The reaction was stirred for 15 minutes after the addition of the last portion and then treated with p-methoxybenzyl chloride (5.32 g, 45.3 mmol) and allowed to stir for 1 hour. The reaction was then quenched by slow addition of excess methanol. After bubbling had stopped, the reaction was poured into water (100 mL) and extracted twice with ethyl acetate. The organics were combined, dried over MgSO4 and the solvent was removed. The residue was purified by silica gel chromatography using a gradient of 0-100% ethyl acetate in hexane to afford 7.1 g (82%) of 5-Fluoro-1-(4-methoxy-benzyl)-1H-indole-2,3-dione; 1H NMR (CDCl3, 400 MHz) δ 3.79 (s, 3H), 4.86 (s, 2H), 6.75 (dd, 1H, J1=3.6, J2=8.6), 6.84-6.90 (m, 2H), 7.19 (ddd, 1H, J1=J2=8.6, J3=3.6), 7.22-7.27 (m, 1H), 7.26-7.31 (m, 2H); HPLC-MS calcd. for C16H12FNO3 (M+H+) 286.1, found 286.3.

Workup

  1. additionafter the addition of the last portion
  2. stirringto stir for 1 hour
  3. customThe reaction was then quenched by slow addition of excess methanol
  4. customAfter bubbling
  5. additionthe reaction was poured into water (100 mL)
  6. extractionextracted twice with ethyl acetate
  7. dry with materialdried over MgSO4
  8. customthe solvent was removed
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-99fd54b087c9445395ee3f31e753d922
Source dataset
uspto-grants-2010_06
Patent number
US07732449B2

Linked notes

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