Triphenylphosphine → Phenyl-[6-(tetrahydrofuran-3-(R)-yl-oxy)quinoxalin-2-yl]amine

HRID 23342

Reaction equation

HRID 23342 reaction equation
[NH:1]([C:8]1[CH:17]=[N:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O[C@H:20]1[CH2:24][CH2:23][O:22][CH2:21]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:2]1([NH:1][C:8]2[CH:17]=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][C@@H:20]4[CH2:24][CH2:23][O:22][CH2:21]4)[CH:14]=3)[N:9]=2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 2733227(S)-(+)-3-HydroxytetrahydrofuranHCID 5462977Diethyl azodicarboxylateHCID 1355124612-Anilino-6-quinoxalinol

Product 1

HCID 22898590Phenyl-[6-(tetrahydrofuran-3-(R)-yl-oxy)quinoxalin-2-yl]amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a THF solution at 0° C. under argon is added 2-anilino-6-quinoxalinol (0.23 g, 0.97 mmol), (S)-(+)-3-hydroxytetrahydrofuran (0.086 mL, 1.3 mmol), and triphenylphosphine (0.31 g, 1.2 mmol). DEAD (0.18 mL, 1.2 mmol) is added portionwise. The reaction is allowed to warm to room temperature and stirred for 1.5 hours. The mixture is concentrated and partitioned between EtOAc and H2O. The organic layer is washed with H2O, brine, dried (MgSO4), and concentrated. The resulting yellow oil is chromatographed (50% EtOAc/hexanes) and taken up in Et2O/IPA. HCl/Et2O solution is added dropwise and the resulting red-orange powder is dried in vacuo. The powder is free-based by stirring in MeOH with washed (3×H2O, 5×MeOHM basic ion exchange resin. The mixture is stirred 30 minutes, filtered, concentrated, and recrystallized from EtOAc/hexanes to provide, in two crops, the product (m.p. 173-175° C.). Anal. Calcd. for C18H17N3O2: C, 70.35; H, 5.57; N, 13.67; Found: C, 70.19; H, 5.60; N, 13.66.

Workup

  1. concentrationThe mixture is concentrated
  2. custompartitioned between EtOAc and H2O
  3. washThe organic layer is washed with H2O, brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe resulting yellow oil is chromatographed (50% EtOAc/hexanes)
  7. additionHCl/Et2O solution is added dropwise
  8. customthe resulting red-orange powder is dried in vacuo
  9. stirringby stirring in MeOH
  10. washwith washed (3×H2O, 5×MeOHM basic ion exchange resin
  11. stirringThe mixture is stirred 30 minutes
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customrecrystallized from EtOAc/hexanes
  15. customto provide, in two crops

Sources & evidence

ORD record
ord-e871bfab0a334f8bb89e79609cb3f075
Source dataset
uspto-grants-2005_02
Patent number
US06852712B2

Linked notes

Loading…