Trifluoroacetic acid → (S)-1-(4-(4-chlorophenoxy)phenyl)-5-(3-(trifluoromethyl)phenyl)imidazolidin-2-one

HRID 1972211Notes

Reaction equation

HRID 1972211 reaction equation
[Cl:1][C:2]1[CH:39]=[CH:38][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)[CH2:16][N:15](CC4C=CC(OC)=CC=4)[C:14]3=[O:37])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=4)[CH2:16][NH:15][C:14]3=[O:37])=[CH:11][CH:12]=2)=[CH:38][CH:39]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59485836(S)-3-[4-(4-chloro-phenoxy)-phenyl]-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one

Product 1

HCID 59485924(S)-1-(4-(4-chlorophenoxy)phenyl)-5-(3-(trifluoromethyl)phenyl)imidazolidin-2-oneYield 91.2%

Procedure

(S)-3-[4-(4-chloro-phenoxy)-phenyl]-1-(4-methoxy-benzyl)-4-(3-trifluoromethyl-phenyl)-imidazolidin-2-one (2.1 g, 3.8 mmol) is treated with TFA (15 mL) at room temperature for 14 h. The excess of TFA is removed under vacuum and the residue is treated with saturated NaHCO3 aqueous solution (50 mL) and extracted with EtOAc (3×100 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%˜70%) to provide the desired product (S)-1-[4-(4-chloro-phenoxy)-phenyl]-5-(3-trifluoromethyl-phenyl)-imidazolidin-2-one as white crystals (1.5 g, 91%). 1H NMR (CDCl3, 400 MHz) δ 7.45˜7.58 (m, 4H), 7.29 (d, 2H), 7.23 (d, 2H), 6.87 (m, 4H), 5.34 (dd, 1H), 4.82 (br, 1H), 4.01 (t, 1H), 3.35 (dd, 1H); HPLC-MS calculated for C22H16ClF3N2O2 (M+H+) 433.1, found 433.1.

Workup

  1. customThe excess of TFA is removed under vacuum
  2. additionthe residue is treated with saturated NaHCO3 aqueous solution (50 mL)
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic layer is washed with brine
  5. dry with materialdried (MgSO4)
  6. customAfter removing the drying agent
  7. concentrationthe solution is concentrated
  8. custompurified by flash column chromatography (silica gel, EtOAc/hexane 0%˜70%)

Sources & evidence

ORD record
ord-b0c1292e2d6d402d922b0f48f2de1b44
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

Loading…