Diethyl Malonate → HCID 136387797, compound

HRID 570743Notes

Reaction equation

HRID 570743 reaction equation
[F:1][C:2]([F:21])([F:20])[CH2:3][CH2:4][C:5](=[NH:19])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=1.[C:22](OCC)(=[O:29])[CH2:23][C:24](OCC)=[O:25].C[O-].[Na+]>COCCO>[OH:29][C:22]1[N:19]=[C:5]([CH2:4][CH2:3][C:2]([F:20])([F:21])[F:1])[N:6]([C:7]2[CH:8]=[CH:9][C:10]([O:13][CH2:14][C:15]([F:17])([F:18])[F:16])=[CH:11][CH:12]=2)[C:24](=[O:25])[CH:23]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 10942334Sodium MethoxideHCID 178511021HCID 178511021, compound

Product 1

HCID 136387797HCID 136387797, compound

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

A mixture of 4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide (20.9 g), diethyl malonate (20.2 mL), sodium methoxide (10.8 g) and 2-methoxyethanol (400 mL) was heated under reflux overnight, and the reaction mixture was concentrated under reduced pressure. Similarly, a mixture of 4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide (22.6 g), diethyl malonate (21.8 mL), sodium methoxide (11.7 g) and 2-methoxyethanol (400 mL) was heated under reflux overnight, and the reaction mixture was concentrated under reduced pressure. The obtained residues were combined, and partitioned between diethyl ether and water. The aqueous layer was separated, to the organic layer was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was suspended in diisopropyl ether. The precipitate was collected by filtration, washed with diisopropyl ether, and dried to give the title compound (41.6 g) as a solid.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux overnight
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. additionSimilarly, a mixture of 4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide (22.6 g), diethyl malonate (21.8 mL), sodium methoxide (11.7 g) and 2-methoxyethanol (400 mL)
  5. temperaturewas heated
  6. temperatureunder reflux overnight
  7. concentrationthe reaction mixture was concentrated under reduced pressure
  8. custompartitioned between diethyl ether and water
  9. customThe aqueous layer was separated, to the organic layer
  10. additionwas added 1N hydrochloric acid
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated under reduced pressure
  15. filtrationThe precipitate was collected by filtration
  16. washwashed with diisopropyl ether
  17. customdried

Sources & evidence

ORD record
ord-83e2d669df0247949cc0aa03d7159f76
Source dataset
uspto-grants-2015_05
Patent number
US09023858B2

Reaction notes

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