Oxalyl chloride → 4-[2-(4-Cyclobutylmethyl-piperazin-1-yl)-2-oxo-ethyl]-3-methyl-benzoic Acid Methyl Ester
Reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9](=[O:21])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[C:12]([CH3:20])[CH:11]=1.Cl.Cl.[CH:24]1([CH2:28][N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:27][CH2:26][CH2:25]1.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C>[CH3:7][O:8][C:9](=[O:21])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([N:32]2[CH2:33][CH2:34][N:29]([CH2:28][CH:24]3[CH2:25][CH2:26][CH2:27]3)[CH2:30][CH2:31]2)=[O:19])=[C:12]([CH3:20])[CH:11]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
Oxalyl chloride (0.36 ml, 3.3 mmol) was added to a solution of 4-carboxymethyl-3-methyl-benzoic acid methyl ester from Example E32 (687 mg, 3.3 mmol) in dichloromethane (20 ml) and few drops of DMF. The mixture was stirred for 3 h at room temperature, concentrated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (10 ml) and added to a solution of 1-cyclobutylmethyl-piperazine dihydrochloride (750 mg, 3.3 mmol) in dichloromethane (10 ml) and DIEA (1.73 ml, 9.9 mmol) at 0° C. The mixture was stirred for 20 h at room temperature and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 3% methanol:97% dichloromethane) to yield the title compound (528 mg, 46%).
Workup
- concentrationconcentrated in vacuo
- customazeotroped with toluene
- dissolutionThe residue was dissolved in dichloromethane (10 ml)
- stirringThe mixture was stirred for 20 h at room temperature
- concentrationconcentrated in vacuo
- customThe residue was purified by flash chromatography on silica gel (eluant; 3% methanol:97% dichloromethane)
Sources & evidence
- ORD record
- ord-bed5290ea06e499fbfbfec43c71cd610
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202858B2
Reaction notes
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