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

HRID 1378731Notes

Reaction equation

HRID 1378731 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 800 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 800 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-c7af8f335bd6455c861a450775afdca4
Source dataset
uspto-grants-1997_09
Patent number
US05668282

Reaction notes

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