Dimethyl malonate → Dimethyl [2-[(2-methylphenoxy)methyl]phenyl]propanedioate

HRID 1601130Notes

Reaction equation

HRID 1601130 reaction equation
[H-].[Na+].[C:3]([O:10][CH3:11])(=[O:9])[CH2:4][C:5]([O:7][CH3:8])=[O:6].I[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:27]>CN1CCCN(C)C1=O>[CH3:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[O:20][CH2:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:4]([C:3]([O:10][CH3:11])=[O:9])[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 193600291-Iodo-2-[(2-methylphenoxy)methyl]benzene

Product 1

HCID 54001010Dimethyl [2-[(2-methylphenoxy)methyl]phenyl]propanedioateYield 79%

Reagents, catalysts & solvents 1

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent2×

Procedure

To a suspension of sodium hydride (60% oil dispersion) (15.4 g) in 90 mL of 1,3-dimethyl-3,4,5,6-tetrahydro-2[1H]-pyrimidinone (DMPU), cooled in an ice-water bath, was added dropwise a solution of dimethyl malonate (44 mL) in DMPU (150 mL). The mixture was stirred 20 minutes after the addition was completed, and then 1-iodo-2 -[(2-methylphenoxy)methyl]benzene (62.5 g) and cuprous iodide (73.3 g) were added. The resulting mixture was stirred at 100° C. for 5 h, then stirred at 25° C. overnight. The mixture was diluted with 1 N. HCl (~150 mL) and extracted with diethyl ether (3×400 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure to a semi-solid, which was purified by flash chromatography on silica get (5:2 hexane:ethyl acetate as eluant). The major material was collected and concentrated to a white solid, which was triturated in hexane and collected by filtration to yield 56.9 g (79% of the title compound of Step C as a white solid, mp 99-103° C.

Workup

  1. temperaturecooled in an ice-water bath
  2. additionafter the addition
  3. stirringThe resulting mixture was stirred at 100° C. for 5 h
  4. stirringstirred at 25° C. overnight
  5. additionThe mixture was diluted with 1 N
  6. extractionHCl (~150 mL) and extracted with diethyl ether (3×400 mL)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure to a semi-solid, which
  10. customwas purified by flash chromatography on silica
  11. customget (5:2 hexane:ethyl acetate as eluant)
  12. customThe major material was collected
  13. concentrationconcentrated to a white solid, which
  14. customwas triturated in hexane
  15. filtrationcollected by filtration

Sources & evidence

ORD record
ord-fa135aab78e54c159b936eb3fde4460b
Source dataset
uspto-grants-1999_11
Patent number
US05977149

Reaction notes

Loading…