Toluene → HCID 178516648, compound

HRID 1088916Notes

Reaction equation

HRID 1088916 reaction equation
[H-].[Na+].C1(C)C=CC=CC=1.[C:10]([NH2:16])(=[O:15])[CH2:11][C:12]([NH2:14])=[O:13].[F:17][C:18]([F:25])([F:24])[C:19](OCC)=O>C(O)CCC>[OH:13][C:12]1[CH:11]=[C:10]([OH:15])[N:16]=[C:19]([C:18]([F:25])([F:24])[F:17])[N:14]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 7911MalonamideHCID 9794Ethyl trifluoroacetateHCID 24758Sodium hydride

Product 1

HCID 178516648HCID 178516648, compoundYield 44.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

Sodium hydride (900 g, 57.5% dispersion in mineral oil; 518 g active NaH; 22.5M) was stirred with 7.5 L toluene in a 22 L round-bottomed flask. Butanol was added over 5 hr. so that the pot temperature was maintained at 40°. The mixture was stirred an additional 16 hr. Malonamide (765 g; 7.5 M) was added, followed by ethyl trifluoroacetate (1065 g; 7.5 M). The ensuing reaction was exothermic; the mixture was then heated on a steam-bath for 3.5 hrs. It was then stirred at 23°-25° for an additional 16 hrs. The mixture was extracted with water (1×4 L and 1×2 L). The combined aqueous extracts were treated with activated charcoal and filtered. The filtrate was maintained at 10°-15° as it was acidified to pH 1-2 with 37% hydrochloric acid. The mixture was chilled to 5°. The solid was isolated by filtration and dried at 50° in vacuo to give 600 g (44.4% yield) VI m.p. 255°-256° (Lit. 265°).

Workup

  1. temperatureso that the pot temperature was maintained at 40°
  2. customThe ensuing reaction
  3. temperaturethe mixture was then heated on a steam-bath for 3.5 hrs
  4. stirringIt was then stirred at 23°-25° for an additional 16 hrs
  5. extractionThe mixture was extracted with water (1×4 L and 1×2 L)
  6. additionThe combined aqueous extracts were treated with activated charcoal
  7. filtrationfiltered
  8. temperatureThe filtrate was maintained at 10°-15° as it
  9. temperatureThe mixture was chilled to 5°
  10. customThe solid was isolated by filtration
  11. customdried at 50° in vacuo

Sources & evidence

ORD record
ord-4556724f4bf345f5bc3d4d5169dd3d38
Source dataset
uspto-grants-1990_10
Patent number
US04963678

Reaction notes

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