Cesium carbonate → 3-(2-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4-{2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-propionic acid tert-butyl ester

HRID 1985209Notes

Reaction equation

HRID 1985209 reaction equation
[C:1]([O:5][C:6](=[O:28])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:16][N:17]1[C:25](=[O:26])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]1=[O:27])([CH3:4])([CH3:3])[CH3:2].[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].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:28])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][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:58])[F:56])=[CH:51][CH:50]=3)[C:31](=[O:59])[N:30]2[CH3:29])=[CH:11][C:10]=1[CH2:16][N:17]1[C:18](=[O:27])[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:25]1=[O:26])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 58979464HCID 58979464, compoundHCID 86596229HCID 86596229, compound

Product 1

HCID 688675093-(2-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4-{2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethoxy}-phenyl)-propionic acid tert-butyl esterYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4-hydroxy-phenyl]-propionic acid tert-butyl ester (57 mg, 0.15 mmol) and Toluene-4-sulfonic acid 2-[3-methyl-2-oxo-1-(4-trifluoromethyl-benzyl)-imidazolidin-4-yl]-ethyl ester (75 mg, 0.16 mmol) in DMF (1 ml) is added Cs2CO3 (64 mg, 0.19 mmol), and the mixture heated at 60° C. for 14 hours. The mixture is cooled, diluted with water (25 ml) and extracted with ethyl acetate (2×25 ml). The combined organic extracts were washed with brine (30 ml), dried (Na2SO4), and concentrated to an oil. Purification by flash chromatography on a Biotage silica cartridge (gradient elution, 5:1 to 1:1 hexanes:acetone) produced an oil (72 mg, 73%).

Workup

  1. temperatureThe mixture is cooled
  2. extractionextracted with ethyl acetate (2×25 ml)
  3. washThe combined organic extracts were washed with brine (30 ml)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated to an oil
  6. customPurification by flash chromatography
  7. washon a Biotage silica cartridge (gradient elution, 5:1 to 1:1 hexanes:acetone)

Sources & evidence

ORD record
ord-ff2b976cba9a4c91a665afbfc3f1f939
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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