1,2-Dichloroethane → 1-(2-Trifluoromethoxyphenylacetyl)-2-carbamoyl-4-(2-methylphenyl)-piperazine

HRID 1740596Notes

Reaction equation

HRID 1740596 reaction equation
[F:1][C:2]([F:15])([F:14])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]([OH:13])=O.[C:16]([CH:19]1[CH2:24][N:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])[CH2:22][CH2:21][NH:20]1)(=[O:18])[NH2:17].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[F:14][C:2]([F:1])([F:15])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]([N:20]1[CH2:21][CH2:22][N:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH3:31])[CH2:24][CH:19]1[C:16](=[O:18])[NH2:17])=[O:13]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27773132-[2-(Trifluoromethoxy)phenyl]acetic acidHCID 154305682-Carbamoyl-4-(2-methylphenyl)piperazine

Product 1

HCID 218372381-(2-Trifluoromethoxyphenylacetyl)-2-carbamoyl-4-(2-methylphenyl)-piperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-trifluoromethoxyphenylacetic acid (0.10 g, 0.48 mmol) from Step 4 above and 2-carbamoyl-4-(2-methylphenyl)piperazine (0.10 g, 0.46 mmol) from Step 4 of Example 1 in DMF (10 mL) was added HOBT (0.075 g, 0.5 mmol), EDC (0.22 g, 0.75 mmol), and DIEA (0.13 mL, 0.75 mmol). The solution was stirred at ambient temperature for 14 h and the solvent was removed under reduced pressure. The residue was partitioned between EtOAc (50 mL) and 0.25 M aqueous citric acid (25 mL). The organic phase was separated and washed with H2O (25 mL), saturated aqueous NaHCO3 (25 mL), and brine (25 mL). The organic phase was dried (MgSO4), filtered, and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography using EtOAc as eluant. The product-containing fractions were evaporated under reduced pressure and the residue was lyophilized from CH3CN:H2O to give the title compound as an amorphous solid.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between EtOAc (50 mL) and 0.25 M aqueous citric acid (25 mL)
  3. customThe organic phase was separated
  4. washwashed with H2O (25 mL), saturated aqueous NaHCO3 (25 mL), and brine (25 mL)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customThe residue was purified by pressurized silica gel column chromatography
  9. customThe product-containing fractions were evaporated under reduced pressure

Sources & evidence

ORD record
ord-5cf8c6cadd914757b55dcc3d6113dc32
Source dataset
uspto-grants-1999_10
Patent number
US05968938

Reaction notes

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