Hydrochloric Acid → N-(2,6-Diisopropyl-phenyl)-malonamic acid

HRID 1013610Notes

Reaction equation

HRID 1013610 reaction equation
C([O:3][C:4](=[O:21])[CH2:5][C:6]([NH:8][C:9]1[C:14]([CH:15]([CH3:17])[CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[CH:18]([CH3:20])[CH3:19])=[O:7])C.CO.[OH-].[Na+].Cl>C(OCC)(=O)C.O.CCCCCCC>[CH:15]([C:14]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:18]([CH3:20])[CH3:19])[C:9]=1[NH:8][C:6](=[O:7])[CH2:5][C:4]([OH:21])=[O:3])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 44375808N-(2,6-Diisopropyl-phenyl)-malonamic acid ethyl ester

Product 1

HCID 19936077N-(2,6-Diisopropyl-phenyl)-malonamic acidYield 93.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

A 5 L 4-necked flask was fitted with a mechanical stirrer and charged with 240.24 g (824 mmol) of the N-(2,6-Diisopropyl-phenyl)-malonamic acid ethyl ester produced immediately above and 1200 mL of methanol. To the clear, orange solution was added 483 mL (966 mmol) of 2.0 N sodium hydroxide. The solution was stirred until HPLC analysis indicated complete reaction (ca. 2.5 h) and then acidified to pH 3 with 3N hydrochloric acid. The suspension was diluted with 2.0 L of ethyl acetate and 0.5 L of water. The aqueous layer was removed and then the organic layer was washed with 0.5 L of water and 0.5 L of brine. The aqueous layers were back-extracted with 0.5 L of ethyl acetate and the combined organic layers were then dried over magnesium sulfate. Evaporation of the solvent at the Rotavap yielded 216 g (99%) of the crude acid as yellowish solids. The crude material was slurried with 2.2 L of heptane and then isolated by filtration. The solids were washed with heptane and petroleum ether and then air-dried giving 202.53 g of the N-(2,6-Diisopropyl-phenyl)-malonamic acid as yellowish solids. HPLC analysis indicated >99% (a/a) purity. The materials 1H-NMR spectrum was consistent with structure.

Workup

  1. customA 5 L 4-necked flask was fitted with a mechanical stirrer
  2. customreaction (ca. 2.5 h)
  3. customThe aqueous layer was removed
  4. washthe organic layer was washed with 0.5 L of water and 0.5 L of brine
  5. extractionThe aqueous layers were back-extracted with 0.5 L of ethyl acetate
  6. dry with materialthe combined organic layers were then dried over magnesium sulfate
  7. customEvaporation of the solvent at the Rotavap
  8. customyielded 216 g (99%) of the crude acid as yellowish solids
  9. customisolated by filtration
  10. washThe solids were washed with heptane and petroleum ether
  11. customair-dried

Sources & evidence

ORD record
ord-f02dec965e2e4c4e81f5d22a573abbde
Source dataset
uspto-grants-2011_07
Patent number
US07981936B2

Reaction notes

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