Cesium carbonate → Methyl 3-(1-methoxypropan-2-yloxy)-5-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)benzoate

HRID 2098327Notes

Reaction equation

HRID 2098327 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH:13]([CH3:17])[CH2:14][O:15][CH3:16])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].I[C:33]1[CH:38]=[CH:37][C:36]([C:39]2[O:40][C:41]([CH3:44])=[N:42][N:43]=2)=[CH:35][CH:34]=1>O1CCOCC1.[Cu](I)I>[CH3:16][O:15][CH2:14][CH:13]([O:12][C:10]1[CH:9]=[C:4]([CH:3]=[C:2]([O:1][C:33]2[CH:34]=[CH:35][C:36]([C:39]3[O:40][C:41]([CH3:44])=[N:42][N:43]=3)=[CH:37][CH:38]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])[CH3:17]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 6765692-(4-Iodophenyl)-5-methyl-[1,3,4]oxadiazoleHCID 67274118Methyl 3-hydroxy-5-(1-methoxypropan-2-yloxy)benzoate2×

Product 1

HCID 67514111Methyl 3-(1-methoxypropan-2-yloxy)-5-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)benzoateYield 67.6%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred suspension of Methyl 3-hydroxy-5-(1-methoxypropan-2-yloxy)benzoate (Intermediate 3) (7.88 g, 32.84 mmol, 1.3 equiv.), N,N-dimethylglycine hydrochloride (1 g, 7.69 mmol. 30 mole %), Cesium carbonate (16.5 g, 50.52 mmol, 2 equiv.), copper (II) iodide (0.488 g, 2.56 mmol, 0.1 mole %) in dry dioxane was added 2-(4-iodophenyl)-5-methyl-1,3,4-oxadiazole (7.2 g, 25.26 mmol, 1 equiv.) under nitrogen. The reaction mixture was heated up to reflux at 100° C. for 24 h. The reaction mixture was cooled, quenched with water and extracted with DCM. Combined organic washings were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo to get the crude product. The crude product was purified by column chromatography using silica gel as stationary phase and EtOAc: petroleum ether as mobile phase to furnish the product (6.8 g) as thick liquid.

Workup

  1. temperatureThe reaction mixture was heated up
  2. temperatureThe reaction mixture was cooled
  3. customquenched with water
  4. extractionextracted with DCM
  5. washCombined organic washings were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto get the crude product
  10. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-d1bdb4056c4f4e3bb1b5afc76360d1fd
Source dataset
uspto-grants-2013_05
Patent number
US08450494B2

Reaction notes

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