Tetrahydrofuran → Ethyl 4-methyl-3-(1-methylphthalazin-6-yl)benzoate

HRID 422549

Reaction equation

HRID 422549 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:20]=[CH:21][C:22]=3[CH3:23])[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1.[CH2:24]1COCC1.CN1CCCC1=O.C[Mg]Br>CCOC(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[CH3:23][C:22]1[CH:21]=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:13][C:12]=1[C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([CH3:24])=[N:3][N:4]=[CH:5]2

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 13387N-methyl-2-pyrrolidoneHCID 59726010Ethyl 3-(1-chlorophthalazin-6-yl)-4-methylbenzoateHCID 178418573HCID 178418573, compound

Product 1

HCID 59726018Ethyl 4-methyl-3-(1-methylphthalazin-6-yl)benzoate

Reagents, catalysts & solvents 2

HCID 5483663Ferric acetylacetonateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A 150-ml round-bottom flask under argon was charged with ethyl 3-(1-chlorophthalazin-6-yl)-4-methylbenzoate (358 mg, 1096 μmol), iron(III) acetylacetonate (38.7 mg, 109.6 □mol), THF (4200 μl), and 1-methyl-2-pyrrolidinone (420 μl). Methylmagnesium bromide (1.4M solution in toluene/tetrahydrofuran (75:25); 1174 μl, 1643 μmol) was then added via a syringe to the resulting orange red suspension, causing an immediate color change to brown, and finally to violet. The resulting mixture was stirred for 10 min, and the reaction (which remained a suspension) was diluted with EtOAc and carefully quenched with a few drops of 10% aqueous HCl solution. The mixture was washed with saturated aqueous NaHCO3 solution and the organic layer was dried (MgSO4), filtered, and concentrated in vacuo. CombiFlash purification (20% to 90% EtOAc in Hexanes) afforded ethyl 4-methyl-3-(1-methylphthalazin-6-yl)benzoate as a light golden brown oil. MS (ES+): 307.1 (M+H)+.

Workup

  1. customthe reaction (which
  2. customcarefully quenched with a few drops of 10% aqueous HCl solution
  3. washThe mixture was washed with saturated aqueous NaHCO3 solution
  4. dry with materialthe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customCombiFlash purification (20% to 90% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-e452b98d6b1042638a46b3596af5928a
Source dataset
uspto-grants-2012_01
Patent number
US08101612B2

Linked notes

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