5-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester dihydrochloride salt → 5-((4-Methylpiperazin-1-YL)methyl)isoindoline

HRID 1486503Notes

Reaction equation

HRID 1486503 reaction equation
Cl.Cl.C(OC([N:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH2:22][N:23]3[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]3)[CH:19]=2)[CH2:14]1)=O)C1C=CC=CC=1.[H][H]>CCO.[Pd]>[CH3:29][N:26]1[CH2:27][CH2:28][N:23]([CH2:22][C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[CH2:14][NH:13][CH2:21]3)[CH2:24][CH2:25]1

Participants

5

Reactant 2

HCID 668965095-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester dihydrochloride saltHCID 178418361HCID 178418361, compound

Product 1

HCID 119558195-((4-Methylpiperazin-1-YL)methyl)isoindolineYield 95%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a degassed solution of 5-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester (Step 9, 1.3 Kg, 3.55 mol) dissolved in EtOH (13 L) was added 10% Pd/C (0.065 Kg). Hydrogen was passed through the mixture at 30° C. for 4 h or until complete by NMR. The solution was then stirred for 1 h under an atmosphere of N2 and then filtered to remove the catalyst through a GF/F filter followed by filtration through a Cuno filter. The filtrate was evaporated to a small volume, azeotroped with toluene (3.9 L) and dried to constant weight yielding the title compound as a red/black oily solid (0.78 Kg) which was stored under nitrogen until required.

Workup

  1. filtrationfiltered
  2. customto remove the catalyst through a GF/F
  3. filtrationfilter
  4. filtrationfollowed by filtration through a Cuno
  5. filtrationfilter
  6. customThe filtrate was evaporated to a small volume
  7. customazeotroped with toluene (3.9 L)
  8. customdried to constant weight

Sources & evidence

ORD record
ord-4899e2b2e2254c15843f395bb86ac9f8
Source dataset
uspto-grants-2016_08
Patent number
US09428439B2

Reaction notes

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