Monoethyl malonate → Ethyl 3-methoxy-4-methoxycarbonylbenzoylacetate

HRID 442791Notes

Reaction equation

HRID 442791 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([OH:5])=O.C([Li])CCC.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[C:26]([O:28][CH3:29])=[O:27])C(Cl)=O>O1CCCC1.CCCCCC.Cl>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=1[C:26]([O:28][CH3:29])=[O:27])[C:3]([CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6])=[O:5]

Participants

7

Reactant 3

HCID 70615Monoethyl malonateHCID 151619683-Methoxy-4-methoxycarbonylbenzoyl chlorideHCID 178418339Butyllithium

Product 1

HCID 53689794Ethyl 3-methoxy-4-methoxycarbonylbenzoylacetate

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of ethyl hydrogen malonate (4.38 g, 33.2 mmol) in dry tetrahydrofuran (100 ml) cooled under an atmosphere of nitrogen to -60° C. with efficient stirring was added a solution of n-butyllithium in hexane (2.5M, 26.5 ml) rapidly dropwise, allowing the temperature to rise to -10° C. during the addition. After stirring the resulting suspension for 15 min at -10° C. it was recooled to -70° C. and a solution of 3-methoxy-4-methoxycarbonylbenzoyl chloride (4.46 g, 19.5 mmol) in dry tetrahydrofuran (30 ml) added dropwise. After addition, the reaction mixture was allowed to warm to room temperature and after 1 h diluted with cold aqueous hydrochloric acid (2M, 35 ml) and ice. The mixture was extracted with diethyl ether (200 ml) and the extract washed twice with a saturated solution of sodium bicarbonate, water and a saturated solution of sodium chloride. The organic layer was dried over magnesium sulphate, filtered and evaporated. The residue was purified on flash silica eluting with dichloromethane to give ethyl 3-methoxy-4-methoxycarbonylbenzoylacetate as an oil.

Workup

  1. additionto rise to -10° C. during the addition
  2. stirringAfter stirring the resulting suspension for 15 min at -10° C. it
  3. customwas recooled to -70° C.
  4. additionAfter addition
  5. extractionThe mixture was extracted with diethyl ether (200 ml)
  6. washthe extract washed twice with a saturated solution of sodium bicarbonate, water
  7. dry with materialThe organic layer was dried over magnesium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified on flash silica eluting with dichloromethane

Sources & evidence

ORD record
ord-3f77f296a0f74d6180ea08ed8755bd36
Source dataset
uspto-grants-1999_04
Patent number
US05891899

Reaction notes

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