Water → Diethyl 2-(4-methoxy-3,5-dimethylbenzoylamino)malonate

HRID 403458Notes

Reaction equation

HRID 403458 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:13])[CH:6]([NH2:12])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH3:3].C(N(CC)CC)C.[CH3:21][O:22][C:23]1[C:31]([CH3:32])=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][C:24]=1[CH3:33].O>ClCCl>[CH2:10]([O:9][C:7](=[O:8])[CH:6]([NH:12][C:27](=[O:28])[C:26]1[CH:30]=[C:31]([CH3:32])[C:23]([O:22][CH3:21])=[C:24]([CH3:33])[CH:25]=1)[C:5]([O:4][CH2:2][CH3:3])=[O:13])[CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 3084143Propanedioic acid, 2-amino-, 1,3-diethyl ester, hydrochloride (1:1)HCID 214353833,5-Dimethyl-4-methoxybenzoyl chloride

Product 1

HCID 67294070Diethyl 2-(4-methoxy-3,5-dimethylbenzoylamino)malonateYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

116.8 g of aminomalonic acid diethyl ester hydrochloride were dissolved in 700 ml of dichloromethane, and 231 ml of triethylamine were added with cooling in an ice bath. A solution of 109.6 g of 4-methoxy-3,5-dimethyl-benzoyl chloride in 400 ml of dichloromethane was slowly added dropwise. After 2 h at 0° C., 200 ml of water were added slowly. The phases were separated, and then the aqueous phase was extracted with 200 ml of dichloromethane twice. The combined organic phases were washed with 2 M hydrochloric acid and subsequently with water, dried with sodium sulfate, filtered and evaporated. The residue was treated with methyl tert-butyl ether, and then the resulting precipitate was isolated by filtration to give 178.7 g of the title compound.

Workup

  1. temperaturewith cooling in an ice bath
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with 200 ml of dichloromethane twice
  4. washThe combined organic phases were washed with 2 M hydrochloric acid and subsequently with water
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. additionThe residue was treated with methyl tert-butyl ether
  9. customthe resulting precipitate was isolated by filtration

Sources & evidence

ORD record
ord-16d4a9c732624b659965449fe495da23
Source dataset
uspto-grants-2014_06
Patent number
US08748436B2

Reaction notes

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