N,N-Dimethylglycine hydrochloride → Methyl 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-(1-methyl-2-oxopyrrolidin-3-yloxy)benzoate

HRID 75964

Reaction equation

HRID 75964 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH:13]2[CH2:17][CH2:16][N:15]([CH3:18])[C:14]2=[O:19])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Cl.CN(C)CC(O)=O.I[C:29]1[CH:34]=[CH:33][C:32]([C:35]2[O:36][C:37]([CH3:40])=[N:38][N:39]=2)=[CH:31][CH:30]=1>O1CCOCC1.[Cu](I)I>[CH3:40][C:37]1[O:36][C:35]([C:32]2[CH:31]=[CH:30][C:29]([O:1][C:2]3[CH:3]=[C:4]([CH:9]=[C:10]([O:12][CH:13]4[CH2:17][CH2:16][N:15]([CH3:18])[C:14]4=[O:19])[CH:11]=3)[C:5]([O:7][CH3:8])=[O:6])=[CH:34][CH:33]=2)=[N:39][N:38]=1

Participants

6

Reactant 3

HCID 75605N,N-Dimethylglycine hydrochlorideHCID 6765692-(4-Iodophenyl)-5-methyl-[1,3,4]oxadiazole2×HCID 66971906Methyl 3-hydroxy-5-(1-methyl-2-oxopyrrolidin-3-yloxy)benzoate2×

Product 1

HCID 66972059Methyl 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-(1-methyl-2-oxopyrrolidin-3-yloxy)benzoateYield 30.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred mixture of Methyl 3-hydroxy-5-(1-methyl-2-oxopyrrolidin-3-yloxy)benzoate (15 g) (Intermediate 3), N,N-dimethylglycine hydrochloride (2.3 g), copper (II) iodide (1 g) in dry 1,4-dioxane was added 2-(4-iodophenyl)-5-methyl-1,3,4-oxadiazole (15.4 g) (Intermediate 4) under nitrogen. The reaction mixture was refluxed 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 ethyl acetate: petroleum ether (9:1) as mobile phase to give the product (7 g) as thick liquid.

Workup

  1. temperatureThe reaction mixture was refluxed for 24 h
  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-5e29f283917d45e2a7c3fd3018e4b0ee
Source dataset
uspto-grants-2014_09
Patent number
US08835469B2

Linked notes

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