4-Carboxymethoxy-3-methyl-benzoic Acid Methyl Ester → 4-{2-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-2-oxo-ethoxy}-3-methyl-benzoic Acid Methyl Ester

HRID 220848Notes

Reaction equation

HRID 220848 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]([OH:14])=O)=[C:6]([CH3:15])[CH:5]=1.Cl.Cl.[CH3:19][C:20]([CH3:30])([CH3:29])[CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>CN(C1C=CN=CC=1)C.ClCCl.C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]([N:26]2[CH2:27][CH2:28][N:23]([CH2:22][CH2:21][C:20]([CH3:30])([CH3:29])[CH3:19])[CH2:24][CH2:25]2)=[O:14])=[C:6]([CH3:15])[CH:5]=1

Participants

6

Reactant 2

HCID 575553254-Carboxymethoxy-3-methyl-benzoic Acid Methyl EsterHCID 670538001-(3,3-Dimethyl-butyl)-piperazine dihydrochloride

Product 1

HCID 670538104-{2-[4-(3,3-Dimethyl-butyl)-piperazin-1-yl]-2-oxo-ethoxy}-3-methyl-benzoic Acid Methyl EsterYield 55%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

WSCD (5.14 g, 27.2 mmol) and DMAP (1.64 g, 13.6 mmol) were added to a solution of 4-carboxymethoxy-3-methyl-benzoic acid methyl ester from Example E41.2 (3.04 g, 13.6 mmol) in dichloromethane (100 ml) and triethylamine (5 ml). The mixture was stirred for 1 h at room temperature then 1-(3,3-dimethyl-butyl)-piperazine dihydro-chloride from Example E4 (3.67 g, 14.9 mmol) was added. The mixture was stirred for 20 h at room temperature then solvents were removed in vacuo. The residue was dissolved in EtOAc, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; EtOAc) to yield the title compound (2.8 g, 55%).

Workup

  1. stirringThe mixture was stirred for 20 h at room temperature
  2. customsolvents were removed in vacuo
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with saturated NaHCO3
  5. dry with materialbrine, dried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel (eluant; EtOAc)

Sources & evidence

ORD record
ord-7f7f9a44bc214835adeb44cf36180ae2
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

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