Dichloromethane → 5-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

HRID 1406807Notes

Reaction equation

HRID 1406807 reaction equation
C(Cl)Cl.[CH3:4][N:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1.[CH2:11]([O:18][C:19]([N:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([CH2:30]OS(C)(=O)=O)[CH:27]=2)[CH2:22]1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>O>[CH2:11]([O:18][C:19]([N:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([CH2:30][N:8]3[CH2:9][CH2:10][N:5]([CH3:4])[CH2:6][CH2:7]3)[CH:27]=2)[CH2:22]1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 531671-MethylpiperazineHCID 579902125-Methanesulfonyloxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

Product 1

HCID 579902085-(4-Methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carboxylic acid benzyl esterYield 47%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

DCM (33 L) and N-methylpiperazine (21.45 L, 193.4 mol) were stirred at 25° C. and the solution from step 8 added over a minimum of 30 mins such that temperature 20-30° C. After stirring the solution for a further 30 mins water (55 L) was added and the organic phase was washed with water (2×55 L). The product was extracted into 0.8M HCl (66 L) and the layers separated. The aqueous phase was washed with DCM (55 L) and then basified with 2M NaOH to pH 10-11 and the product was extracted into EtOAc (2×55 L). The combined organic phase were filtered to remove solids and the evaporated followed by azeotroping with toluene and drying to constant weight to give the title compound, 6.63 kg (47% yield, 98% pure by hplc).

Workup

  1. additionwas added
  2. washthe organic phase was washed with water (2×55 L)
  3. extractionThe product was extracted into 0.8M HCl (66 L)
  4. customthe layers separated
  5. washThe aqueous phase was washed with DCM (55 L)
  6. extractionthe product was extracted into EtOAc (2×55 L)
  7. filtrationThe combined organic phase were filtered
  8. customto remove solids
  9. customby azeotroping with toluene
  10. customdrying to constant weight

Sources & evidence

ORD record
ord-4c6390376b86456096d76f511d586d1c
Source dataset
uspto-grants-2014_12
Patent number
US08916552B2

Reaction notes

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