Toluene-4-sulfonic acid 2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethyl ester → 3-{4-[2-(1-Benzyl-3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-(2-fluoro-phenoxy)-2-methyl-propionic acid

HRID 1985138Notes

Reaction equation

HRID 1985138 reaction equation
C(=O)([O-])[O-].[Cs+].C([O:8][C:9](=[O:46])[C:10]([O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[F:45])([CH3:37])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH:21]2[CH2:25][N:24]([CH2:26][C:27]3[CH:32]=[CH:31][C:30](OC)=[CH:29][CH:28]=3)[C:23](=[O:35])[N:22]2[CH3:36])=[CH:14][CH:13]=1)C.[Cs+].C(OC(=O)C(OC1C=CC=CC=1F)(C)CC1C=CC(O)=CC=1)C.COC1C=CC(CN2CC(CCOS(C3C=CC(C)=CC=3)(=O)=O)N(C)C2=O)=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH2:26]([N:24]1[CH2:25][CH:21]([CH2:20][CH2:19][O:18][C:15]2[CH:16]=[CH:17][C:12]([CH2:11][C:10]([O:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[F:45])([CH3:37])[C:9]([OH:46])=[O:8])=[CH:13][CH:14]=2)[N:22]([CH3:36])[C:23]1=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 57719164Toluene-4-sulfonic acid 2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethyl esterHCID 577192632-(2-Fluorophenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl esterHCID 867608772-(2-Fluoro-phenoxy)-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl ester Cesium carbonate

Product 1

HCID 102891963-{4-[2-(1-Benzyl-3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-(2-fluoro-phenoxy)-2-methyl-propionic acidYield 35,777,556%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Fluoro-phenoxy)-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl ester Cesium carbonate (6.12 g, 18.76 nmol) is added to a solution of 2-(2-Fluoro-phenoxy)-3-(4-hydroxy-phenyl)-2-methyl-propionic acid ethyl ester 1.99 g, 6.26 mmol) and toluene-4-sulfonic acid 2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethyl ester (2.88 g, 6.88 mmol) in DMF (20 mL). The resultant mixture is stirred at 65° C. under an atmosphere of nitrogen for 18 h, then diluted with ethyl acetate. The organic layer is washed with 1N HCl, water, and brine. The organic layer is dried over MgSO4, concentrated in vacuo, and purified by flash column chromatography (17% acetone in hexanes) to provide the title compound (3.4 g, 97%). 1H NMR (400 MHz, CDCl3): δ 7.19 (d, 2H, J=5.4 Hz), 7.17 (d, 2H, J=5.4 Hz), 7.07-7.01 (m, 1H), 6.97-6.87 (m, 3H), 6.83 (d, 2H, J=8.6 Hz), 6.74 (d, 2H, J=8.6 Hz), 4.32, 4.28 (ABq, 2H, J=14.6 Hz), 4.20 (q, 2H, J=7.5 Hz), 3.94 (t, 2H, J=5.9 Hz), 3.77 (s, 3H), 3.60-3.53 (m, 1H), 3.33 (t, 1H, J=8.6 Hz), 3.26, 3.14 (ABq, 2H, J=14.0 Hz), 2.92 (t, 1 h, J=8.6 Hz), 2.82 (s, 3H), 2.24-2.17 (m, 1H), 1.89-1.82 (m, 1H), 1.38 (s, 3H), 1.23 (t, 3H, J=7.5 Hz). MS [EI+] 565 (M+H)+. Rf=0.48 in 50% acetone in hexanes.

Workup

  1. washThe organic layer is washed with 1N HCl, water, and brine
  2. dry with materialThe organic layer is dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. custompurified by flash column chromatography (17% acetone in hexanes)

Sources & evidence

ORD record
ord-f18f7379543c4b06b0b9f8a424d2ef2a
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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