2-Bromopropan-1-ol → 7-Nitro-2-Isopropyl-4-bromo-2H-phthalazin-1-one

HRID 1783656Notes

Reaction equation

HRID 1783656 reaction equation
[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8]([Br:15])=[N:9][NH:10][C:11]2=[O:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].[H-].[Na+].Br[CH:19]([CH3:22])[CH2:20]O>CN(C)C=O>[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8]([Br:15])=[N:9][N:10]([CH:19]([CH3:22])[CH3:20])[C:11]2=[O:14])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 117132-Bromopropan-1-olHCID 24758Sodium hydride2×HCID 211065897-Nitro-4-bromo-2H-phthalazin-1-one

Product 1

HCID 211065877-Nitro-2-Isopropyl-4-bromo-2H-phthalazin-1-oneYield 200.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

7-Nitro-4-bromo-2H-phthalazin-1-one (84 g, 0.31 mol) was dissolved in dimethylformamide (DMF) (400 ml). To this was added NaH (60%, 7.5 g, 0.31 mol) as a DMF suspension (200 ml). The mixture was stirred at RT for 30 min then 2-bromo-propanol (7.7 g, 62 mmol) was added in one portion as a solution in DMF (250 ml). The reaction mixture was stirred for 24 hours whereupon LC-MS showed 40% starting material remaining. To this was added NaH (3.75 g 0.15 mol) and the reaction stirred for a further 24 hours. The DMF was removed under vacuum and the resulting crude material purified by successive column chromatography (elution: 92% heptane to 8% EtOAc) to give the title compound (38.8 g, 40% yield) as a light yellow solid. 1H-NMR: (400 MHz, D6-DMSO), 8.88 (1H, d), 8.87 (1H, dd), 8.16 (1 H, d), 5.19 (1H, m), 1.13 (6H, d).

Workup

  1. stirringThe reaction mixture was stirred for 24 hours whereupon LC-MS
  2. stirringthe reaction stirred for a further 24 hours
  3. customThe DMF was removed under vacuum
  4. customthe resulting crude material purified by successive column chromatography (elution: 92% heptane to 8% EtOAc)

Sources & evidence

ORD record
ord-bc96dc780e294cfc97da8f03327e0fdb
Source dataset
uspto-grants-2009_03
Patent number
US07501410B2

Reaction notes

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