tert-Butyl hydroperoxide → 1-(3-Methylanilino)-4-([1,3,5]trioxan-2-yl)phthalazine

HRID 2054182Notes

Reaction equation

HRID 2054182 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[N:8][N:7]=1.[O:19]1[CH2:24][O:23][CH2:22][O:21][CH2:20]1.FC(F)(F)C(O)=O.C(OO)(C)(C)C>C(#N)C.O>[CH3:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH:20]2[O:21][CH2:22][O:23][CH2:24][O:19]2)=[N:8][N:7]=1

Participants

7

Reactant 4

HCID 6410tert-Butyl hydroperoxideHCID 6422Trifluoroacetic acidHCID 80811,3,5-TrioxaneHCID 223864691-(3-Methylanilino)phthalazine

Product 1

HCID 223864601-(3-Methylanilino)-4-([1,3,5]trioxan-2-yl)phthalazine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 9.6 g (40.8 mmol) 1-(3-methylanilino)phthalazine and 173 g 1,3,5-trioxane in 570 ml acetonitrile, 3.12 ml (40.8 mmol) trifluoroacetic acid, 11.0 ml (80% in tBuOOtBu; 87.4 mmol) tBuOOH and 190 mg (0.68 mmol) FeSO4.7 H2O are added, and the mixture stirred for 17 h at 80° C. The cooled reaction mixture is partly evaporated in the RE, diluted with EtOAc and water and adjusted to an alkaline pH with 1 N NaOH. The aqueous phase is separated off and twice extracted with EtOAc. The organic phases are washed twice with water and brine, dried (Na2SO4) and evaporated. Column chromatography (SiO2; EtOAc/toluene 1:3; applied as solution in dichloromethane/acetone 9:1) yields the title compound after crystallization with the addition of DIPE; m.p. 161° C.; DC (EtOAc/toluene 1:3) Rf=0.27; 1H-NMR (DMSO-d6) 9.27 (s, HN), 8.74 (m, 1H), 8.61 (m, 1H), 8.00 (m, 2H), 7.72 (s, 1H), 7.68 (d, 1H), 7.25 (t, 1H), 6.89 (d, 1H), 6.39 (s, 1H), 5.47 (d, 2H), 5.41 (d, 2H), 2.33 (s, 3H); FAB-MS (M+H)+=324; anal. calc.(C18H17N3O3) C, 66.86%; H, 5.30%; N, 13.00%; meas. C, 66.83%; H, 5.36%; N, 12.81%.

Workup

  1. customThe cooled reaction mixture
  2. customis partly evaporated in the RE
  3. additiondiluted with EtOAc and water
  4. customThe aqueous phase is separated off
  5. extractiontwice extracted with EtOAc
  6. washThe organic phases are washed twice with water and brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated

Sources & evidence

ORD record
ord-06d11aa3aba7448b910aaf93f1253e2a
Source dataset
uspto-grants-2008_02
Patent number
US07329660B2

Reaction notes

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