Cesium carbonate → 3-(4-{2-[3-(4-Methoxy-benzyl)-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl ester

HRID 1985162Notes

Reaction equation

HRID 1985162 reaction equation
[C:1](=[O:4])([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:9][C:10](=[O:28])[C:11]([CH3:27])([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[CH3:8].[CH3:29][N:30]1[CH:34]([CH2:35][CH2:36]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:33][N:32]([CH2:48][C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=2)[C:31]1=[O:59]>CN(C=O)C.C(OCC)(=O)C>[CH2:7]([O:9][C:10](=[O:28])[C:11]([CH3:27])([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:36][CH2:35][CH:34]2[CH2:33][N:32]([CH2:48][C:49]3[CH:54]=[CH:53][C:52]([C:55]([F:57])([F:56])[F:58])=[CH:51][CH:50]=3)[C:31](=[O:59])[N:30]2[CH2:29][C:13]2[CH:18]=[CH:17][C:16]([O:4][CH3:1])=[CH:15][CH:14]=2)=[CH:15][CH:14]=1)[CH3:8]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11220314Ethyl 3-(4-hydroxyphenyl)-2-methyl-2-phenoxypropionateHCID 86596229HCID 86596229, compound

Product 1

HCID 688698823-(4-{2-[3-(4-Methoxy-benzyl)-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl esterYield 194.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cesium carbonate (2.18 g, 6.702 mmol) is added to a solution of 3-(4-Hydroxy-phenyl)-2-methyl-2-phenoxy-propionic acid ethyl ester (1.55 g, 5.155 mmol) and Toluene-4-sulfonic acid 2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethyl ester (3.19 g, 5.67 mmol) in DMF (30 mL). The resultant mixture is stirred at 55° C. under an atmosphere of nitrogen for 18 h, then diluted with ethyl acetate. The organic layer is washed, then dried, concentrated, and purified by flash chromatography (17% acetone in hexanes) to provide the title compound (3.46 g, 97%). 1H NMR (400 MHz, CDCl3): δ 7.57 (d, 2H, J=7.01 Hz), 7.37 (d, 2H, J=7.1 Hz), 7.23-7.19 (m, 4H), 7.13 (d, 2H, J=8.7 Hz), 6.97 (t, 1H, J=7.1 Hz), 6.87-6.80 (m, 4H), 6.67 (d, 2H, J=8.7 Hz), 4.79, 4.07 (ABq, 2H, J=15.0 Hz), 4.47, 4.43 (ABq, 2H, J=15.0 Hz), 4.20 (q, 2H, J=7.1 Hz), 3.92-3.87 (m, 2H), 3.80 (s, 3H), 3.61-3.55 (m, 1H), 3.31 (t, 2H, J=8.7 Hz), 3.24, 3.10 (ABq, 2H, J=14.2 Hz), 3.00 (t, 1H, J=7.9 Hz), 2.21-2.14 (m, 1H), 1.87-1.78 (m, 1H), 1.38 (s, 3H), 1.21 (t, 3H, J=7.1 Hz). MS [EI+] 691 (M+H)+. Rf=0.49 in 50% acetone in hexanes.

Workup

  1. washThe organic layer is washed
  2. customdried
  3. concentrationconcentrated
  4. custompurified by flash chromatography (17% acetone in hexanes)

Sources & evidence

ORD record
ord-763cebc0e4ec432cbc3e8948b3864fa1
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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