1,2-Dichloroethane → N-{2-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]ethyl}-3-methoxy-N-methylterephthalamic Acid Methyl Ester

HRID 907640

Reaction equation

HRID 907640 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([O:13][CH3:14])[CH:5]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH3:39][NH:40][CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][CH:46]([O:49][C:50](=[O:64])[NH:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=2[C:58]2[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=2)[CH2:45][CH2:44]1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:15])[C:4]1[CH:12]=[CH:11][C:7]([C:8]([N:40]([CH2:41][CH2:42][N:43]2[CH2:44][CH2:45][CH:46]([O:49][C:50](=[O:64])[NH:51][C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=3[C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)[CH2:47][CH2:48]2)[CH3:39])=[O:10])=[C:6]([O:13][CH3:14])[CH:5]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 566436031-(2-(Methylamino)ethyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamateHCID 593403342-Methoxy-4-(methoxycarbonyl)benzoic acid

Product 1

HCID 59340332N-{2-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]ethyl}-3-methoxy-N-methylterephthalamic Acid Methyl EsterYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-methoxyterephthalic acid 4-methyl ester (450 mg, 2.1 mmol; prepared as described in Preparation 18) in DMF (10 mL) was added EDC (630 mg, 3.3 mmol), HOAt (2.4 mL, 1.18 mmol, 0.5M in DMF) and DIPEA (1.3 mL, 7.05 mmol). When the mixture was homogenous, a solution of biphenyl-2-ylcarbamic acid 1-(2-methylaminoethyl)piperidin-4-yl ester (830 mg, 2.4 mmol; prepared as described in Preparation 4) was added slowly. The reaction mixture was stirred at room temperature for 16 hours and then washed with water (100 mL), 1N HCl (100 mL), 1N NaOH (100 mL), brine (100 mL), dried over MgSO4, filtered and concentrated to afford the title intermediate in 89% yield (1.04 g, 1.9 mmol). MS m/z: [M+H+] calcd for C31H35N3O6, 545.6. found, 546.6.

Workup

  1. washwashed with water (100 mL), 1N HCl (100 mL), 1N NaOH (100 mL), brine (100 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-ecde6b1c90cf458db9333e5ca49a793f
Source dataset
uspto-grants-2011_09
Patent number
US08013152B2

Linked notes

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