Toluene → 7,8,9,10-Tetrahydro-8-methyl-2,3-bis(phenylmethoxy)-pyrido[4,3-f]quinoxalin-6-yl phosphonic acid diethyl ester

HRID 48245

Reaction equation

HRID 48245 reaction equation
Br[C:2]1[C:3]2[CH2:19][N:18]([CH3:20])[CH2:17][CH2:16][C:4]=2[C:5]2[N:6]=[C:7]([O:14][CH3:15])[C:8]([O:12][CH3:13])=[N:9][C:10]=2[CH:11]=1.[CH2:21]([O:23][P:24]([O-:28])[O:25][CH2:26][CH3:27])[CH3:22].C(N([CH2:34][CH3:35])CC)C.[C:36]1(C)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O(C(C)C)C(C)C>[CH2:21]([O:23][P:24]([C:2]1[C:3]2[CH2:19][N:18]([CH3:20])[CH2:17][CH2:16][C:4]=2[C:5]2[N:6]=[C:7]([O:14][CH2:15][C:35]3[CH:34]=[CH:10][CH:11]=[CH:2][CH:3]=3)[C:8]([O:12][CH2:13][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[N:9][C:10]=2[CH:11]=1)(=[O:28])[O:25][CH2:26][CH3:27])[CH3:22]

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 3780918DiethylphosphiteHCID 100657006-Bromo-7,8,9,10-tetrahydro-2,3-dimethoxy-8-methyl-pyrido[4,3-f]quinoxaline

Product 1

HCID 231936707,8,9,10-Tetrahydro-8-methyl-2,3-bis(phenylmethoxy)-pyrido[4,3-f]quinoxalin-6-yl phosphonic acid diethyl esterYield 36%

Reagents, catalysts & solvents 1

HCID 7914Diisopropyl EtherSolvent

Procedure

A solution of the product from Example 100 (1.83 g, 3.73 mmol) was dissolved in dry toluene and treated with diethylphosphite (0.72 mL, 5.59 mmol), triethylamine (1.56 mL, 11.2 mmol) and tetrakis (triphenylphosphine)palladium (0) (0.44 g, 0.37 mmol). The resulting solution was heated to reflux under a nitrogen atmosphere for 48 hours. The reaction mixture was concentrated and the residue was dissolved in CHCl3 and washed with saturated aqueous NaHCO3 solution. The organic phase was dried, filtered and concentrated. The residue was purified by chromatography (SiO2, gradient elution EtOAc then 5:1 EtOAc/EtOH). The material obtained was dissolved in hot iPr2O, filtered and concentrated. The residue was then broken up in a mall amount of iPr2O and the solid collected by filtration and dried under vacuum to give the title compound as a yellow solid (0.74 g, 36% yield), mp=104° C. The filtrates were concentrated to give an additional 0.77 g of the title compound.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux under a nitrogen atmosphere for 48 hours
  3. concentrationThe reaction mixture was concentrated
  4. dissolutionthe residue was dissolved in CHCl3
  5. washwashed with saturated aqueous NaHCO3 solution
  6. customThe organic phase was dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (
  10. washSiO2, gradient elution EtOAc
  11. customThe material obtained
  12. filtrationfiltered
  13. concentrationconcentrated
  14. filtrationthe solid collected by filtration
  15. customdried under vacuum

Sources & evidence

ORD record
ord-7482237cc7c148efbe1f2a6d9e039668
Source dataset
uspto-grants-2004_03
Patent number
US06703391B2

Linked notes

Loading…