Anisole → HCID 67161115, compound

HRID 469664Notes

Reaction equation

HRID 469664 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].BrC1C=C2C(=CC=1)C(=O)OC2=O.[C:17]1([O:23][CH3:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.BrC1C=CC(C(O)=O)=C(C(=O)C2C=CC(OC)=CC=2)C=1.BrC1C=CC(C(=O)C2C=CC(OC)=CC=2)=C(C=1)C(O)=O.O.NN.BrC1C=C2C(=CC=1)C(=O)N[N:73]=C2C1C=CC(OC)=CC=1.[Br:88][C:89]1[CH:98]=[C:97]2[C:92]([C:93](C3C=CC(OC)=CC=3)=[N:94][NH:95][C:96]2=[O:99])=[CH:91][CH:90]=1.C1(P(ON)(C2C=CC=CC=2)=O)C=CC=CC=1>ClCCCl.CCO.C1COCC1>[NH2:73][N:95]1[N:94]=[C:93]([C:20]2[CH:21]=[CH:22][C:17]([O:23][CH3:24])=[CH:18][CH:19]=2)[C:92]2[C:97](=[CH:98][C:89]([Br:88])=[CH:90][CH:91]=2)[C:96]1=[O:99]

Participants

13

Reactant 9

HCID 7519AnisoleHCID 24654Hydrazine hydrate (1:1)HCID 665904-Bromophthalic anhydrideHCID 6451240Aluminum(III) ChlorideHCID 10955453O-(Diphenylphosphinyl)hydroxylamineHCID 67160577HCID 67160577, compoundHCID 67160578HCID 67160578, compoundHCID 67161565HCID 67161565, compoundHCID 67161628HCID 67161628, compound

Product 1

HCID 67161115HCID 67161115, compound

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of AlCl3 and 5-bromoisobenzofuran-1,3-dione in 1,2-dichloroethane was briefly heated to form a solution, and cooled to room temperature. Anisole was added dropwise and stirred overnight. The mixture was quenched with 1N HCl, extracted with dichloromethane, dried (Na2SO4), filtered, and triturated (Hexanes/Et2O) to give a ˜1:1 mixture of 4-bromo-2-(4-methoxybenzoyl)benzoic acid:5-bromo-2-(4-methoxybenzoyl)benzoic acid as a white solid. A solution of this material and hydrazine hydrate in EtOH was heated at 60° C. overnight, concentrated, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried (Na2SO4), and chromatographed (15-50% (1:1 EtOAc:dichloromethane)/hexanes) to give a mixture of 6-bromo-4-(4-methoxyphenyl)phthalazin-1(2H)-one and 7-bromo-4-(4-methoxyphenyl)phthalazin-1(2H)-one as a white solid. A solution of this mixture in THF was treated with O-(diphenylphosphoryl)hydroxylamine using a method similar to that described in Example 1B, and the regioisomers separated upon purification by chromatography on SiO2 (7% EtOAc/dichloromethane) to give the title compound. 1H NMR (300 MHz, DMSO) δ 8.45 (d, J=2.1, 1H), 8.05 (dd, J=8.7, 2.2, 1H), 7.69 (d, J=8.7, 1H), 7.59-7.48 (m, 2H), 7.17-7.07 (m, 2H), 6.55 (d, J=6.1, 2H), 3.85 (s, 3H).

Workup

  1. temperaturewas briefly heated
  2. customto form a solution
  3. customThe mixture was quenched with 1N HCl
  4. extractionextracted with dichloromethane
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customtriturated (Hexanes/Et2O)
  8. customto give
  9. concentrationconcentrated
  10. additiondiluted with EtOAc
  11. washwashed with saturated aqueous NaHCO3 and brine
  12. dry with materialdried (Na2SO4)
  13. customchromatographed (15-50% (1:1 EtOAc:dichloromethane)/hexanes)
  14. customto give
  15. customthe regioisomers separated upon purification by chromatography on SiO2 (7% EtOAc/dichloromethane)

Sources & evidence

ORD record
ord-f3f76ce29e61409a84a70a60d680cafe
Source dataset
uspto-grants-2014_01
Patent number
US08629143B2

Reaction notes

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