Acetamidomalonic acid diethyl ester → Diethyl acetamido(6-octyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)propanedioate

HRID 1921685Notes

Reaction equation

HRID 1921685 reaction equation
[H-].[Na+].[C:3]([NH:6][CH:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])(=[O:5])[CH3:4].Br[CH:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH:25]=2)[C:20]1=[O:37]>CN(C=O)C>[CH2:11]([O:10][C:8](=[O:9])[C:7]([NH:6][C:3](=[O:5])[CH3:4])([CH:19]1[CH2:28][CH2:27][C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH:25]=2)[C:20]1=[O:37])[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH3:12]

Participants

5

Reactant 3

HCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 534010322-Bromo-6-octyl-3,4-dihydronaphthalen-1(2H)-one

Product 1

HCID 57577370Diethyl acetamido(6-octyl-1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl)propanedioateYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (720 mg, 18.0 mmol) 60% in mineral oil was suspended in dry DMF (10 mL) and a solution of diethyl acetamidomalonate (3.26 g, 15 mmol) in dry DMF (10 mL) was added. The solution was stirred at 0° C. for 3 hours until the anion had formed. A solution of 4 (2.02 g, 6.0 mmol) in dry DMF (10 mL) was added and the solution warmed to room temperature and stirred overnight. The mixture was poured into distilled water (50 mL), in an ice-bath, acidified to pH 3 with 1M hydrochloric acid and extracted with ethyl acetate (3×50 mL). The organic phases were washed with brine (2×30 mL) and dried over magnesium sulfate and concentrated under vacuum. The residue was purified by column chromatography (Silica gel, 40% EtOAc in hexanes) to provide 2.12 g of compound 5 (75%).

Workup

  1. customhad formed
  2. temperaturethe solution warmed to room temperature
  3. stirringstirred overnight
  4. additionThe mixture was poured
  5. distillationinto distilled water (50 mL)
  6. customin an ice-bath, acidified to pH 3 with 1M hydrochloric acid
  7. extractionextracted with ethyl acetate (3×50 mL)
  8. washThe organic phases were washed with brine (2×30 mL)
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under vacuum
  11. customThe residue was purified by column chromatography (Silica gel, 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f94fe5295966405998e6aca498d052c3
Source dataset
uspto-grants-2012_05
Patent number
US08173710B2

Reaction notes

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