Sodium hydride → HCID 20729420, compound

HRID 910068Notes

Reaction equation

HRID 910068 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]1=2.[H-].[Na+].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:1]1[CH2:7][CH2:6][CH2:5][CH2:4][C:3]2[CH:8]=[CH:9][CH:10]=[CH:11][C:2]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, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add 2,3,4,5-tetrahydro-1H-benzo[b]azepine in small portions to a 0° C. suspension of 60% sodium hydride (3.0 g, 0.12 mol) in 300 mL of dimethylformamide. Upon complete addition of the amine, remove the ice bath and stir the reaction at 20-24° C. for 40 minutes. Add ethyl bromopyruvate (22.6 mL, 0.16 mol) and stir the resulting mixture at 20-24° C. for 6 hours. Add an additional 5 mL of ethyl bromopyruvate and stir the mixture for 1 hour. Quench by adding 50 mL of water then dilute with 1.5 L of dichloromethane. Separate the layers, wash the organic layer sequentially with water (2×500 mL) and saturated aqueous sodium chloride (500 mL), dry over sodium sulfate, filter, and concentrate under reduced pressure at 60° C. Dissolve the residue in ethyl acetate (500 ml), wash sequentially with water (3×100 mL) and saturated aqueous sodium chloride, dry over sodium sulfate, filter, and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 5-10% EtOAc/hexanes to provide the desired compound as an off white solid (7.0 g, 40%).

Workup

  1. customremove the ice bath
  2. customthe reaction at 20-24° C. for 40 minutes
  3. stirringstir the mixture for 1 hour
  4. customQuench
  5. additionby adding 50 mL of water
  6. additionthen dilute with 1.5 L of dichloromethane
  7. customSeparate the layers
  8. washwash the organic layer sequentially with water (2×500 mL) and saturated aqueous sodium chloride (500 mL)
  9. dry with materialdry over sodium sulfate
  10. filtrationfilter
  11. concentrationconcentrate under reduced pressure at 60° C
  12. dissolutionDissolve the residue in ethyl acetate (500 ml)
  13. washwash sequentially with water (3×100 mL) and saturated aqueous sodium chloride
  14. dry with materialdry over sodium sulfate
  15. filtrationfilter
  16. concentrationconcentrate under reduced pressure
  17. washeluting with 5-10% EtOAc/hexanes

Sources & evidence

ORD record
ord-81d460cc3bee4c298e5ae0f1804ccbb2
Source dataset
uspto-grants-2011_09
Patent number
US08022065B2

Reaction notes

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