1,2-Dichloroethane → HCID 131721413, compound

HRID 1740617Notes

Reaction equation

HRID 1740617 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][C:22]([OH:24])=O)=[C:17]([O:25][C:26]([F:29])([F:28])[F:27])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:30]([CH:33]1[CH2:38][N:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[CH2:36][CH2:35][NH:34]1)(=[O:32])[NH2:31].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[F:29][C:26]([F:28])([F:27])[O:25][C:17]1[CH:16]=[C:15]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH:20]=[CH:19][C:18]=1[CH2:21][C:22]([N:34]1[CH2:35][CH2:36][N:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[CH2:38][CH:33]1[C:30](=[O:32])[NH2:31])=[O:24]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 154305682-Carbamoyl-4-(2-methylphenyl)piperazineHCID 18700088HCID 18700088, compound

Product 1

HCID 131721413HCID 131721413, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(N-tert-butyloxy-carbonyl-4-piperidinyloxy)-2-(trifluoromethoxy)phenylacetic acid (0.50 g, 1.15 mmol) from Step 9 above and 2-carbamoyl-4-(2-methyl-phenyl)piperazine (0.28 g, 1.1 mmol) from Step 4 of Example 1 in DMF (20 mL) was added HOBT (0.175 g, 1.15 mmol), EDC (0.53 g, 1.8 mmol), and DIEA (0.26 mL, 1.5 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 (100 mL) and 0.25 M aqueous citric acid (75 mL). The organic phase was separated and washed with H2O (25 mL), saturated aqueous NaHCO3 (75 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 to give 1-(1-(2-trifluoromethoxy-4-(N-tert-butyoxycarbonyl-4-piperidinyloxy)phenylacetyl)-2-carbamoyl-4-(2-methylphenyl)piperazine as an amorphous solid (HPLC retention time=11 min (method A); TLC Rf =0.5 (7:3 EtOAc:hexanes).

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was partitioned between EtOAc (100 mL) and 0.25 M aqueous citric acid (75 mL)
  3. customThe organic phase was separated
  4. washwashed with H2O (25 mL), saturated aqueous NaHCO3 (75 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-763c9a57890d434cb6e696e7ae3b4906
Source dataset
uspto-grants-1999_10
Patent number
US05968938

Reaction notes

Loading…