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

HRID 376838Notes

Reaction equation

HRID 376838 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.Cl>[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

6

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 2

HCID 313Hydrochloric AcidSolventHCID 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 gel (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. extractionextracted with diethyl ether (3×400 mL)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure to a semi-solid, which
  9. customwas purified by flash chromatography on silica gel (5:2 hexane: ethyl acetate as eluant)
  10. customThe major material was collected
  11. concentrationconcentrated to a white solid, which
  12. customwas triturated in hexane
  13. filtrationcollected by filtration

Sources & evidence

ORD record
ord-4d78685d07394f93ae6b21eb4c37dfd6
Source dataset
uspto-grants-2000_02
Patent number
US06022870

Reaction notes

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