Sodium hydride → HCID 20729420, compound

HRID 983924Notes

Reaction equation

HRID 983924 reaction equation
[H-].[Na+].[NH:3]1[CH2:9][CH2:8][CH2:7][CH2:6][C:5]2[CH:10]=[CH:11][CH:12]=[CH:13][C:4]1=2.Br[CH2:15][C:16](=[O:22])[C:17]([O:19][CH2:20][CH3:21])=[O:18]>CN(C)C=O>[CH2:20]([O:19][C:17](=[O:18])[C:16](=[O:22])[CH2:15][N:3]1[CH2:9][CH2:8][CH2:7][CH2:6][C:5]2[CH:10]=[CH:11][CH:12]=[CH:13][C:4]1=2)[CH3:21]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 66144Ethyl bromopyruvate2×HCID 5765032,3,4,5-tetrahydro-1H-1-benzazepine

Product 1

HCID 20729420HCID 20729420, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22 °C

Procedure

To a 0° C. suspension of 60% sodium hydride (3.0 g, 0.12 mol) in 300 mL of dimethylformamide was added 2,3,4,5-tetrahydro-1H-benzo[b]azepine in small portions. Upon complete addition of the amine, the ice bath was removed and the reaction stirred at 20-24° C. for 40 minutes. Ethyl bromopyruvate (22.6 mL, 0.16 mol) was then added and the resulting mixture stirred at 20-24° C. for 6 hours. An additional 5 mL of ethyl bromopyruvate was added and the mixture stirred for 1 hour. The reaction was quenched by the addition of 50 mL of water followed by dilution with 1.5 L of dichloromethane. The layers were separated and the organic layer was washed with water (2×500 mL) and saturated aqueous sodium chloride (500 mL). The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure at 60° C. The residual brown oil was dissolved in ethyl acetate (500 mL) and was washed 3 times with water (100 mL) and once with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel chromatography, eluting with 5-10% EtOAc/hexanes to provide 7.0 g (40%) of the desired compound as an off white solid.

Workup

  1. customthe ice bath was removed
  2. stirringthe resulting mixture stirred at 20-24° C. for 6 hours
  3. stirringthe mixture stirred for 1 hour
  4. customThe reaction was quenched by the addition of 50 mL of water
  5. customThe layers were separated
  6. washthe organic layer was washed with water (2×500 mL) and saturated aqueous sodium chloride (500 mL)
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure at 60° C
  10. dissolutionThe residual brown oil was dissolved in ethyl acetate (500 mL)
  11. washwas washed 3 times with water (100 mL)
  12. dry with materialonce with saturated aqueous sodium chloride, dried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. washeluting with 5-10% EtOAc/hexanes

Sources & evidence

ORD record
ord-0cb9bc057b1646b2994ada7e12c1a69f
Source dataset
uspto-grants-2005_03
Patent number
US06867198B2

Reaction notes

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