Cesium carbonate → 3-{2-Methyl-4-[4-phenoxymethyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-phenyl}-propionic acid methyl ester

HRID 854554Notes

Reaction equation

HRID 854554 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([SH:12])=[CH:8][C:7]=1[CH3:13].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:22][C:23]1[S:27][C:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[N:25][C:24]=1[CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C(#N)C>[CH3:1][O:2][C:3](=[O:14])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([S:12][CH2:22][C:23]2[S:27][C:26]([C:28]3[CH:29]=[CH:30][C:31]([C:34]([F:35])([F:36])[F:37])=[CH:32][CH:33]=3)=[N:25][C:24]=2[CH2:38][O:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[CH:8][C:7]=1[CH3:13]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 541446143-(4-Mercapto-2-methyl-phenyl)-propionic Acid Methyl EsterHCID 589341045-Chloromethyl-4-phenoxymethyl-2-(4-trifluoromethyl-phenyl)-thiazole

Product 1

HCID 694712153-{2-Methyl-4-[4-phenoxymethyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-phenyl}-propionic acid methyl esterYield 34.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-(4-Mercapto-2-methyl-phenyl)-propionic acid-methyl ester (126 mg, 0.600 mmol) is dissolved into anhydrous acetonitrile (ACN) (2 mL). Cesium carbonate (326 mg, 1.00 mmol) is added to the reaction, followed by the addition of 5-Chloromethyl-4-phenoxymethyl-2-(4-trifluoromethyl-phenyl)-thiazole (200 mg, 0.5211 mmol). The reaction is allowed to stir under nitrogen at room temperature and monitored by TLC and HPLC. Upon complete consumption of the chloride, the reaction is diluted with diethyl ether and quenched with 0.1N NaOH. The two phases are separated, then the organic layer washed with water and brine. The organic phase is dried over anhydrous sodium sulfate and concentrated under vacuum. The residue is further purified using either EtOAc/Hexanes (1:9) or Acetone/Hexanes (1:9) gradients on silica gel chromatography to yield 3-{2-Methyl-4-[4-phenoxymethyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethylsulfanyl]-phenyl}-propionic acid methyl ester (100 mg, 0.1796 mmol) or 30%.

Workup

  1. customUpon complete consumption of the chloride
  2. additionthe reaction is diluted with diethyl ether
  3. customquenched with 0.1N NaOH
  4. customThe two phases are separated
  5. washthe organic layer washed with water and brine
  6. dry with materialThe organic phase is dried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue is further purified

Sources & evidence

ORD record
ord-da89aafe8b394d19b0fa0e74f39360f7
Source dataset
uspto-grants-2007_08
Patent number
US07259175B2

Reaction notes

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