p-Toluenesulfonic acid → 6-Fluoro-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one

HRID 1736673Notes

Reaction equation

HRID 1736673 reaction equation
C[O:2][C:3](=O)[C:4]([CH3:17])([CH3:16])[NH:5][C:6]1[CH:11]=[C:10]([F:12])[CH:9]=[CH:8][C:7]=1[N+:13]([O-])=O.[H][H].C1(C)C=CC(S(O)(=O)=O)=CC=1>[Pd].CO>[F:12][C:10]1[CH:11]=[C:6]2[C:7](=[CH:8][CH:9]=1)[NH:13][C:3](=[O:2])[C:4]([CH3:17])([CH3:16])[NH:5]2

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 22912865N-(5-Fluoro-2-nitrophenyl)-2-methylalanine methyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 229128926-Fluoro-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

A mixture of N-(5-fluoro-2-nitrophenyl)-2-methylalanine methyl ester (XI, EXAMPLE 7, 11.2 g), palladium on carbon (10%, 0.63 g), and methanol (350 ml) is shaken under 44 psi of hydrogen pressure for 1.5 hr. Additional palladium on carbon (10%, 0.23 g) is added and the mixture is shaken at 36 psi for another 45 min. p-Toluenesulfonic acid (0.46 g) is added and the catalyst is filtered off. The filtrate is concentrated to about 150 ml and warmed at 80° for 75 min. The solvent is then removed under reduced pressure and the residue is chromatographed on silica gel (700 ml) eluting with dichloromethane/methanol (98/2). aaa a solid. The product is crystallized from methanol/dichloromethane/hexane to give the title compound, mp 148.5°-149.0°; NMR (CDCl3) 1.42, 3.80, 6.40, 6.46, 6.66 and 8.35 δ.

Workup

  1. additionis added
  2. filtrationthe catalyst is filtered off
  3. concentrationThe filtrate is concentrated to about 150 ml
  4. temperaturewarmed at 80° for 75 min
  5. customThe solvent is then removed under reduced pressure
  6. customthe residue is chromatographed on silica gel (700 ml)
  7. washeluting with dichloromethane/methanol (98/2)
  8. customThe product is crystallized from methanol/dichloromethane/hexane

Sources & evidence

ORD record
ord-1168388e31674e7da350a4257da07b87
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

Loading…