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

HRID 633611Notes

Reaction equation

HRID 633611 reaction equation
Cl.[NH2:2][CH:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:4]([O:6][CH2:7][CH3:8])=[O:5].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>[CH3:21][O:22][C:23]1[C:24]([CH3:33])=[CH:25][C:26]([C:27]([NH:2][CH:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:28])=[CH:30][C:31]=1[CH3:32]

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)malonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

58.4 g of diethyl aminomalonate hydrochloride were suspended in 300 ml of dichloromethane, and 115 ml of triethylamine were added with ice cooling. At 0° C., 54.8 g of 4-methoxy-3,5-dimethylbenzoyl chloride in 250 ml of dichloromethane were then added dropwise. After 2 hours at 0° C., 100 ml of water were added dropwise, and the aqueous phase was separated off and extracted with 200 ml of dichloromethane. The combined organic phases were extracted first with 2M aqueous hydrochloric acid and then with water, dried over sodium sulfate, filtered and concentrated. The residue was triturated with methyl tert-butyl ether, filtered off with suction and dried under reduced pressure. This gave 89.3 g (96%) of the title compound which was reacted further without any further purification.

Workup

  1. customthe aqueous phase was separated off
  2. extractionextracted with 200 ml of dichloromethane
  3. extractionThe combined organic phases were extracted first with 2M aqueous hydrochloric acid
  4. dry with materialwith water, dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was triturated with methyl tert-butyl ether
  8. filtrationfiltered off with suction
  9. customdried under reduced pressure
  10. customThis gave 89.3 g (96%) of the title compound which was reacted further without any further purification

Sources & evidence

ORD record
ord-14d820cb479b4378a9649a4dc203eda0
Source dataset
uspto-grants-2016_04
Patent number
US09321787B2

Reaction notes

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