Potassium Iodide → [rac]-3-{4-[2-(2-Chloro-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-methyl-phenyl}-ethoxy-propionic acid ethyl ester

HRID 479225Notes

Reaction equation

HRID 479225 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[CH2:9]([O:11][C:12](=[O:26])[CH:13]([O:23][CH2:24][CH3:25])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][C:16]=1[CH3:22])[CH3:10].Cl[CH2:28][C:29]1[N:30]=[C:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[Cl:41])[O:32][C:33]=1[CH3:34].ClC1C=CC=CC=1C=O.O=P(Cl)(Cl)Cl>CC(C)=O>[CH2:9]([O:11][C:12](=[O:26])[CH:13]([O:23][CH2:24][CH3:25])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:28][C:29]2[N:30]=[C:31]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[Cl:41])[O:32][C:33]=2[CH3:34])=[CH:17][C:16]=1[CH3:22])[CH3:10]

Participants

8

Reactant 6

HCID 4875Potassium IodideHCID 69962-ChlorobenzaldehydeHCID 10796Cesium carbonateHCID 24813Phosphorus oxychlorideHCID 219742564-(Chloromethyl)-2-(2-chlorophenyl)-5-methyloxazoleHCID 57792490[Rac]-2-ethoxy-3-(4-hydroxy-2-methyl-phenyl)-propionic acid ethyl ester

Product 1

HCID 69557833[rac]-3-{4-[2-(2-Chloro-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-methyl-phenyl}-ethoxy-propionic acid ethyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Cesium carbonate (97 mg, 300 μmol, 1.5 eq.) and a trace of potassium iodide were added to a solution of [rac]-2-ethoxy-3-(4-hydroxy-2-methyl-phenyl)-propionic acid ethyl ester (50 mg, 200 μmol, 1 eq., example 129 c]) and 4-chloromethyl-2-(2-chloro-phenyl)-5-methyl-oxazole (72 mg, 300 μmol, 1.5 eq., prepared from 2-chloro-benzaldehyde and diacetyl monoxyme followed by treatment with POCl3 in analogy to the procedures described in examples 21 a] and b]) in acetone (4 ml). The mixture was heated under reflux for 12 h, filtered off and the filtrate evaporated in vacuo. The residue was taken up in ethyl acetate and ice cold 1 M hydrochloric acid. The organic layer was washed two times with brine and dried over sodium sulfate. Removal of the solvent under reduced pressure gave a yellow oil which was purified by column chromatography (silica gel, hexane/AcOEt=9/1) to give 72 mg (160 μmol, 79%) of the title compound as colorless oil.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 12 h
  3. filtrationfiltered off
  4. customthe filtrate evaporated in vacuo
  5. washThe organic layer was washed two times with brine
  6. dry with materialdried over sodium sulfate
  7. customRemoval of the solvent under reduced pressure
  8. customgave a yellow oil which
  9. customwas purified by column chromatography (silica gel, hexane/AcOEt=9/1)

Sources & evidence

ORD record
ord-781b0b2cf57c412285186fb4792cd588
Source dataset
uspto-grants-2003_11
Patent number
US06642389B2

Reaction notes

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