N-Methylphthalimide → 4-isopropylphthalazin-1(2H)-one

HRID 469514Notes

Reaction equation

HRID 469514 reaction equation
[CH:1]([Mg]Br)([CH3:3])[CH3:2].C[N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=O.O.[NH2:19]N>C1COCC1>[CH:1]([C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:15](=[O:16])[NH:7][N:19]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 11074N-MethylphthalimideHCID 24654Hydrazine hydrate (1:1)HCID 178418365HCID 178418365, compound

Product 1

HCID 109762454-isopropylphthalazin-1(2H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of isopropylmagnesium bromide in THF (1M, 6.4 mL, 6.4 mmol) was added to a solution of 2-methylisoindoline-1,3-dione (0.793 g, 4.92 mmol) in THF (15 mL) at 0° C., stirred for 15 minutes, concentrated, dissolved in EtOH (12 mL) with a catalytic amount of concentrated HCl. Hydrazine hydrate (0.58 mL, 15 mmol) was added, and mixture was microwaved at 180° C. for 30 minutes, concentrated, and chromatographed on SiO2 (33% EtOAc/hexane) to give the title compound as a white solid (0.591 g, 3.14 mmol). 1H NMR (300 MHz, DMSO-d6) δ 12.47 (s, 1H), 8.28 (dd, 1H), 8.06 (d, 1H), 7.94 (ddd, 1H), 7.85 (ddd, 1H), 3.57 (quin, 1H), 1.27 (d, 6H); LC/MS (APCI) M/Z 189.1 (M+H)+.

Workup

  1. concentrationconcentrated
  2. dissolutiondissolved in EtOH (12 mL) with a catalytic amount of concentrated HCl
  3. custommixture was microwaved at 180° C. for 30 minutes
  4. concentrationconcentrated
  5. customchromatographed on SiO2 (33% EtOAc/hexane)

Sources & evidence

ORD record
ord-bbb6797b162a4dfc89d77d6d93a8629e
Source dataset
uspto-grants-2014_01
Patent number
US08629143B2

Reaction notes

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