2-Bromopropan-1-ol → Bromo-3-isopropyl-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid ethyl ester

HRID 1765354Notes

Reaction equation

HRID 1765354 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([Br:16])=[N:11][NH:10][C:9]2=[O:17])=[O:5])[CH3:2].[H-].[Na+].Br[CH:21]([CH3:24])[CH2:22]O>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([Br:16])=[N:11][N:10]([CH:21]([CH3:24])[CH3:22])[C:9]2=[O:17])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 117132-Bromopropan-1-olHCID 24758Sodium hydrideHCID 57856207Bromo-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid ethyl ester

Product 1

HCID 68898772Bromo-3-isopropyl-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid ethyl esterYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

Bromo-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid ethyl ester (6 g, 0.02 mol) was dissolved in dimethylformamide (DMF) (60 ml). To this was added NaH (60%, 0.97 g, 0.024 mol) as a DMF suspension (5 ml). The mixture was stirred at room temperature for 30 minutes then 2-bromo-propanol (3.7 g, 0.03 mol) was added in one portion as a solution in DMF (5 ml). The reaction mixture was stirred for 48 hours whereupon LC-MS showed complete consumption of starting material. The DMF was removed under vacuum and the resulting residue was partitioned between DCM (100 ml) and water (100 ml), the organic layer was dried (MgSO4), filtered and concentrated under vacuum. The resulting yellow oil was recrystallised from methanol to give the title compound (2.3 g, 34% yield) as a white solid. MS (ESI+)=(M+H)+ 339 & 341

Workup

  1. stirringThe reaction mixture was stirred for 48 hours whereupon LC-MS
  2. customconsumption of starting material
  3. customThe DMF was removed under vacuum
  4. customthe resulting residue was partitioned between DCM (100 ml) and water (100 ml)
  5. dry with materialthe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe resulting yellow oil was recrystallised from methanol

Sources & evidence

ORD record
ord-027f3739a9e9442ebf1e033f9635527c
Source dataset
uspto-grants-2007_06
Patent number
US07226923B2

Reaction notes

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