3-Bromo-1-methylpyrrolidin-2-one → Methyl 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-(1-methyl-2-oxopyrrolidin-3-yloxy)benzoate

HRID 75970Notes

Reaction equation

HRID 75970 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[O:20][C:21]([CH3:24])=[N:22][N:23]=3)=[CH:15][CH:14]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].Br[CH:26]1[CH2:30][CH2:29][N:28]([CH3:31])[C:27]1=[O:32]>CN(C=O)C>[CH3:24][C:21]1[O:20][C:19]([C:16]2[CH:15]=[CH:14][C:13]([O:12][C:10]3[CH:9]=[C:4]([CH:3]=[C:2]([O:1][CH:26]4[CH2:30][CH2:29][N:28]([CH3:31])[C:27]4=[O:32])[CH:11]=3)[C:5]([O:7][CH3:8])=[O:6])=[CH:18][CH:17]=2)=[N:23][N:22]=1

Participants

4

Reactant 2

HCID 111829543-Bromo-1-methylpyrrolidin-2-one2×HCID 66972201Methyl 3-hydroxy-5-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)benzoate2×

Product 1

HCID 66972059Methyl 3-(4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy)-5-(1-methyl-2-oxopyrrolidin-3-yloxy)benzoateYield 100.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of Methyl 3-hydroxy-5-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]benzoate (4 g) (Intermediate 7) in dry DMF, 3-Bromo-1-methyl-pyrrolidine-2-one (4.12 g) (Intermediate 5) [J. Med. Chem., 1987, 30, 1995-98] was added under nitrogen atmosphere at room temperature in three portions at 4 h interval. The reaction mixture was stirred at room temperature for 16 h and then warmed to 45-50° C. for 3 h. The reaction was monitored by TLC. After completion, reaction mixture was diluted with ice cold water and extracted with EtOAc. All organic layers were combined and washed with water, brine, dried over anhydrous sodium sulphate, filtered and concentrated under vacuum to get crude thick liquid product. Crude residue was chromatographed to yield pure compound (5.2 g).

Workup

  1. temperaturewarmed to 45-50° C. for 3 h
  2. customAfter completion, reaction mixture
  3. additionwas diluted with ice cold water
  4. extractionextracted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customto get crude thick liquid product
  10. customCrude residue was chromatographed

Sources & evidence

ORD record
ord-53dc81a1f2914bbd962e5017c13b1e08
Source dataset
uspto-grants-2014_09
Patent number
US08835469B2

Reaction notes

Loading…