Cesium carbonate → HCID 86640215, compound

HRID 2081041Notes

Reaction equation

HRID 2081041 reaction equation
[CH3:1][N:2]1[CH:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][NH:4][C:3]1=[O:14].Br[C:16]1[C:17]([Cl:22])=[N:18][CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:22][C:17]1[C:16]([N:4]2[CH2:5][CH:6]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[N:2]([CH3:1])[C:3]2=[O:14])=[CH:21][CH:20]=[CH:19][N:18]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6933243-Bromo-2-chloropyridineHCID 671035641,1-Dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate

Product 1

HCID 86640215HCID 86640215, compoundYield 57.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1,1-dimethylethyl 3-methyl-2-oxo-4-imidazolidinecarboxylate (650 mg, 3.25 mmol) (prepared as described in step (iii) of Example 13, starting from (4S)-2-oxo-3-{[(phenylmethyl)oxy]carbonyl}-4-imidazolidinecarboxylic acid) and 3-bromo-2-chloropyridine (625 mg, 3.25 mmol) in 1,4-dioxane (30 ml) was added cesium carbonate (4231 mg, 12.98 mmol), tris(dibenzylideneacetone)dipalladium(0) (149 mg, 0.162 mmol) and Xantphos™ (141 mg, 0.243 mmol) and the reaction stirred at reflux overnight. The reaction mixture was allowed to cool and solvent was removed under vacuum and the residue partitioned between ethyl acetate and water. The organic layer was separated and washed with saturated sodium hydrogen carbonate solution, water and brine and separated by hydrophobic frit. The organic solution was reduced under vacuum and the residue purified by SP4 automated silica gel chromatography eluting with 10-80% ethyl acetate in iso-hexane to give 1,1-dimethylethyl 1-(2-chloro-3-pyridinyl)-3-methyl-2-oxo-4-imidazolidinecarboxylate (579 mg, 51.5% yield)

Workup

  1. temperatureat reflux overnight
  2. temperatureto cool
  3. customsolvent was removed under vacuum
  4. customthe residue partitioned between ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with saturated sodium hydrogen carbonate solution, water and brine
  7. customseparated by hydrophobic frit
  8. customthe residue purified by SP4 automated silica gel chromatography
  9. washeluting with 10-80% ethyl acetate in iso-hexane

Sources & evidence

ORD record
ord-cc01ecff491c432d8af35c53bc8ba7d9
Source dataset
uspto-grants-2011_04
Patent number
US07932282B2

Reaction notes

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