3-(4-Nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione → Lenalidomide

HRID 514975Notes

Reaction equation

HRID 514975 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13])([O-])=O.[H][H]>[Pd].CN(C=O)C>[CH:11]1[CH:10]=[C:9]2[C:8](=[O:13])[N:7]([CH:14]3[C:15](=[O:21])[NH:16][C:17](=[O:20])[CH2:18][CH2:19]3)[CH2:6][C:5]2=[C:4]([NH2:1])[CH:12]=1

Participants

5

Reactant 2

HCID 114717813-(4-Nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 216326Lenalidomide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
62.5 °C

Procedure

Into a 5.0 L 4 necked RB flask, charged 100.0 g of 3-(4-nitro-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione, 10.0 g of 10% Pd/C and 3200 ml of DMF under nitrogen atmosphere. Stirred the mass and raise the reaction mass temperature to 60-65° C. Started the hydrogen gas bubbling into reaction mass at temperature 60-65° C. for 6 hours. The progress of the reaction is monitored by TLC. Cooled the mass to temperature 25 to 30° C. Filtered the catalyst Pd/C under plant vacuum in the presence of nitrogen atmosphere and wash with dimethylformamide; wet Pd/C is transferred into a polyethene bag for recovery. Distilled off the above organic layer solvent completely under vacuum below 60° C. Charged ethyl acetate 800 ml (lot-I) to the mass and stirred for 60 min. Filtered the solid and wash with 200 mL of ethyl acetate (Lot-II). Dried the above wet material in a oven at temperature 65-75° C. for 120-180 min. Dried Weight of the compound is 78.0 g.

Workup

  1. custombubbling into reaction mass at temperature 60-65° C. for 6 hours
  2. temperatureCooled the mass to temperature 25 to 30° C
  3. filtrationFiltered the catalyst Pd/C under plant vacuum in the presence of nitrogen atmosphere
  4. washwash with dimethylformamide
  5. distillationDistilled off the above organic layer solvent completely under vacuum below 60° C
  6. stirringCharged ethyl acetate 800 ml (lot-I) to the mass and stirred for 60 min
  7. filtrationFiltered the solid
  8. washwash with 200 mL of ethyl acetate (Lot-II)
  9. customDried the above wet material in a oven at temperature 65-75° C. for 120-180 min

Sources & evidence

ORD record
ord-e39f0e4f112f48b29871b3f460e4d378
Source dataset
uspto-grants-2015_08
Patent number
US09108945B2

Reaction notes

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