Potassium Carbonate → HCID 86662034, compound

HRID 591786Notes

Reaction equation

HRID 591786 reaction equation
[OH:1][C:2]1[C:9]([CH3:10])=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[CH3:11].C([O-])([O-])=O.[K+].[K+].Br[CH2:19][C@H:20]1[NH:24][C:23](=[O:25])[CH2:22][CH2:21]1>CN(C=O)C>[CH3:10][C:9]1[CH:8]=[C:5]([CH:4]=[C:3]([CH3:11])[C:2]=1[O:1][CH2:19][C@@H:20]1[CH2:21][CH2:22][C:23](=[O:25])[NH:24]1)[CH:6]=[O:7]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 11229111(5S)-5-(Bromomethyl)pyrrolidin-2-one

Product 1

HCID 86662034HCID 86662034, compoundYield 5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-hydroxy-3,5-dimethylbenzaldehyde (2.65 g, 17.7 mmol) in DMF (100 mL) was added K2CO3 (3.66 g, 26.6 mmol). The mixture was stirred at room temperature under nitrogen for 30 minutes. Then, a solution of (S)-5-(bromomethyl)pyrrolidin-2-one (3.15 g, 17.7 mmol) in DMF (100 mL) was added, and the mixture heated at reflux for 16 hours. The mixture was then concentrated, ethyl acetate (250 mL) added, and the organic phase washed sequentially with water (2×150 mL), and brine (200 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography, eluting with 100% ethyl acetate to 10% MeOH/ethyl acetate, followed by a second chromatography, eluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH, to afford (S)-3,5-dimethyl-4-((5-oxopyrrolidin-2-yl)methoxy)benzaldehyde as a white solid (0.200 g, 5%).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 16 hours
  3. concentrationThe mixture was then concentrated
  4. additionethyl acetate (250 mL) added
  5. washthe organic phase washed sequentially with water (2×150 mL), and brine (200 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 100% ethyl acetate to 10% MeOH/ethyl acetate
  11. washeluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH

Sources & evidence

ORD record
ord-dfa59ca9dbb142cca7445fade43d5563
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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