Phthalimide → HCID 66980463, compound

HRID 1038822Notes

Reaction equation

HRID 1038822 reaction equation
CS(O[CH2:6][C:7]1([F:20])[CH2:12][CH2:11][N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1)(=O)=O.[C:21]1(=[O:31])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[NH:22]1.CC([O-])(C)C.[K+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-]>[CH2:13]([N:10]1[CH2:11][CH2:12][C:7]([CH2:6][N:22]2[C:23](=[O:30])[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:21]2=[O:31])([F:20])[CH2:8][CH2:9]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 6809PhthalimideHCID 23665647Potassium tert-butoxideHCID 86665106HCID 86665106, compound

Product 1

HCID 66980463HCID 66980463, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

The (1-benzyl-4-fluoropiperidin-4-yl)methyl methanesulfonate (1.82 g, 6.04 mmol, Preparation #V.1) was dissolved in DMF (18 mL) and isoindoline-1,3-dione (1.07 g, 7.25 mmol), Bu4NI (1.12 g, 3.02 mmol) and KOtBu (1.36 g, 12.1 mmol) were added. The resulting mixture was stirred at about 100° C. for about 12 h. The mixture was cooled to rt and concentrated under reduced pressure. The residue was diluted with water (10 mL) and extracted with Et2O (3×10 mL). The combined organic layers were washed with brine (2×20 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 0 to 10% MeOH/DCM to afford 2-((1-benzyl-4-fluoropiperidin-4-yl)methyl)isoindoline-1,3-dione (0.8 g, 38%): LC/MS (Table 2, Method f) Rt=2.21 min; MS m/z 353 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with water (10 mL)
  4. extractionextracted with Et2O (3×10 mL)
  5. washThe combined organic layers were washed with brine (2×20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with a gradient of 0 to 10% MeOH/DCM

Sources & evidence

ORD record
ord-72696ab109fd4f0dbeb4b313b58922b5
Source dataset
uspto-grants-2013_10
Patent number
US08551981B2

Reaction notes

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