Oxalyl chloride → 4-{3-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-3-oxo-propyl}-3-methyl-benzoic Acid Methyl Ester

HRID 220860Notes

Reaction equation

HRID 220860 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([OH:20])=O)=[C:12]([CH3:21])[CH:11]=1.Cl.[CH3:24][C:25]([CH3:35])([CH3:34])[CH2:26][CH2:27][N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C>[CH3:7][O:8][C:9](=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]([N:31]2[CH2:32][CH2:33][N:28]([CH2:27][CH2:26][C:25]([CH3:35])([CH3:34])[CH3:24])[CH2:29][CH2:30]2)=[O:20])=[C:12]([CH3:21])[CH:11]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 231123491-(3,3-Dimethyl-butyl)-piperazine hydrochlorideHCID 57555260Methyl 4-(2-carboxyethyl)-3-methylbenzoate

Product 1

HCID 575554114-{3-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-3-oxo-propyl}-3-methyl-benzoic Acid Methyl EsterYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (2.6 ml, 30 mmol) was added slowly to a solution of 4-(2-carboxy-ethyl)-3-methyl-benzoic acid methyl ester from Example E30.3 (5.33 g, 24 mmol) in di-chloromethane (60 ml) and few drops of DMF at 0° C. The mixture was stirred for 2 h at room temperature then concentrated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (30 ml) and added to a solution of 1-(3,3-dimethyl-butyl)-piperazine hydrochloride from Example E4 (6.3 g, 26 mmol) in dichloromethane (45 ml) and DIEA (17 ml, 96 mmol) at 0° C. The mixture was stirred for 1 h at room temperature then concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 5% methanol:95% dichloromethane) to yield the title compound (8.5 g, 96%).

Workup

  1. customat 0° C
  2. concentrationthen concentrated in vacuo
  3. customazeotroped with toluene
  4. dissolutionThe residue was dissolved in dichloromethane (30 ml)
  5. stirringThe mixture was stirred for 1 h at room temperature
  6. concentrationthen concentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (eluant; 5% methanol:95% dichloromethane)

Sources & evidence

ORD record
ord-62913286c04f4280bc4b03ce67f278a5
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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