Sodium hydride → HCID 57908784, compound

HRID 606550Notes

Reaction equation

HRID 606550 reaction equation
[H-].[Na+].[C:3]([NH:6][CH:7]([C:12]([O:14][CH3:15])=[O:13])[C:8]([O:10][CH3:11])=[O:9])(=[O:5])[CH3:4].Br[CH:17]1[CH2:23][CH2:22][CH2:21][C:20]2[CH:24]=[C:25]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH:26]=[CH:27][C:19]=2[C:18]1=[O:36]>CN(C=O)C>[CH3:11][O:10][C:8](=[O:9])[C:7]([NH:6][C:3](=[O:5])[CH3:4])([CH:17]1[CH2:23][CH2:22][CH2:21][C:20]2[CH:24]=[C:25]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH:26]=[CH:27][C:19]=2[C:18]1=[O:36])[C:12]([O:14][CH3:15])=[O:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 291813Dimethyl acetamidomalonateHCID 57908779HCID 57908779, compound

Product 1

HCID 57908784HCID 57908784, compoundYield 15.2%

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 dimethyl acetamidomalonate (3.00 g, 15 mmol) in dry DMF (10 mL) was added. The solution was stirred at 0° C. for 3 h until the anion had formed. A solution of 4 (2.12 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), acidified to pH 3 with 1M hydrochloric acid in an ice-bath and extracted into 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 give 0.420 g compound 5 (15%). 1H NMR (300 MHz, CDCl3) δ 0.85 (t, 3H, J=6.22 Hz), 1.24 (m, 10H), 1.58 (p, 2H, J=6.95 Hz), 1.97 (s, 3H), 2.45-2.60 (m, 4H), 2.83-3.21 (m, 4H), 3.88 (dd, 1H, J=14.00 Hz, 3.68 Hz), 4.05 (s, 6H), 6.86 (s, 1H), 7.03 (s, 1H), 7.07 (d, 1H, J=8.69 Hz), 7.84 (d, 1H, J=8.36 Hz).

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. customacidified to pH 3 with 1M hydrochloric acid in an ice-bath
  7. extractionextracted into 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-2fe152a61a2f4c09b197abf4cc8759a1
Source dataset
uspto-grants-2011_03
Patent number
US07915315B2

Reaction notes

Loading…