Potassium Phosphate, Tribasic → (S)-3-[4-(4-chloro-phenoxy)-phenyl]-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one

HRID 1972210Notes

Reaction equation

HRID 1972210 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[CH2:12][C@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)[NH:10][C:9]2=[O:23])=[CH:5][CH:4]=1.[Cl:26][C:27]1[CH:40]=[CH:39][C:30]([O:31][C:32]2[CH:37]=[CH:36][C:35](I)=[CH:34][CH:33]=2)=[CH:29][CH:28]=1.CN[C@@H]1CCCC[C@H]1NC.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Cu]I>[Cl:26][C:27]1[CH:40]=[CH:39][C:30]([O:31][C:32]2[CH:37]=[CH:36][C:35]([N:10]3[C@@H:11]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[CH:14]=4)[CH2:12][NH:8][C:9]3=[O:23])=[CH:34][CH:33]=2)=[CH:29][CH:28]=1.[Cl:26][C:27]1[CH:40]=[CH:39][C:30]([O:31][C:32]2[CH:37]=[CH:36][C:35]([N:10]3[C@@H:11]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:21])([F:22])[F:20])[CH:14]=4)[CH2:12][N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:25][CH:24]=4)[C:9]3=[O:23])=[CH:34][CH:33]=2)=[CH:29][CH:28]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 193519901-Chloro-4-(4-iodophenoxy)benzeneHCID 59485847(S)-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one

Product 2

HCID 59485836(S)-3-[4-(4-chloro-phenoxy)-phenyl]-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-oneYield 156.3%HCID 59485924(S)-1-(4-(4-chlorophenoxy)phenyl)-5-(3-(trifluoromethyl)phenyl)imidazolidin-2-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of (S)-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one (1.7 g, 4.86 mmol), 4-(4-clorophenoxy)-iodobenzene, (1.77 g, 5.35 mmol), CuI (93 mg, 0.49 mmol), trans-N,N′-dimethyl-cyclohexane-1,2-diamine (119 mg, 0.97 mmol) and K3PO4 (2.06 g, 9.72 mmol) in DMF (17 mL) is degassed and heated to 110° C. under N2 for 16 h. After cooling down to room temperature, the mixture was poured into water (200 mL) and extracted with EtOAc (3×50 mL). The combined organic layer is washed with brine and dried (MgSO4). After removing the drying agent, the solution is concentrated and purified by flash column chromatography (silica gel, EtOAc/hexane 0%˜80%) to provide the desired product (S)-3-[4-(4-chloro-phenoxy)-phenyl]-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one (example 154) as a white solid (2.1 g, 78%). 1H NMR (CDCl3, 400 MHz) δ 7.51 (m, 2H), 7.44 (m, 2H), 7.34 (d, 2H), 7.23 (m, 4H), 6.87 (m, 6H), 5.17 (dd, 1H), 4.53 (d, 1H), 4.37 (d, 1H), 3.79 (s, 3H), 3.76 (t, 1H), 3.07 (dd, 1H); HPLC-MS calculated for C30H24ClF3N2O3 (M+H+) 553.1, found 553.1.

Workup

  1. customis degassed
  2. temperatureAfter cooling down to room temperature
  3. additionthe mixture was poured into water (200 mL)
  4. extractionextracted with EtOAc (3×50 mL)
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried (MgSO4)
  7. customAfter removing the drying agent
  8. concentrationthe solution is concentrated
  9. custompurified by flash column chromatography (silica gel, EtOAc/hexane 0%˜80%)

Sources & evidence

ORD record
ord-7e34876f647b47fa9b79424b24dacc90
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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