Sulfuric Acid → 7-Hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

HRID 516257Notes

Reaction equation

HRID 516257 reaction equation
N[C:2]1[CH:17]=[CH:16][C:5]2[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:10][C:4]=2[CH:3]=1.S(=O)(=O)(O)[OH:19]>N([O-])=O.[Na+]>[OH:19][C:2]1[CH:17]=[CH:16][C:5]2[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:10][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 584948787-Amino-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

Product 1

HCID 584953637-Hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 23668193Sodium NitriteSolvent

Procedure

To ethyl 7-amino-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate was added a 5% aqueous sulfuric acid solution, followed by stirring under ice-cooling. An aqueous solution (30 ml) of 10.22 g of sodium nitrite was added dropwise in portions thereto, and followed by stirring at the same temperature for 0.5 hours and then stirring at 60° C. for 3 hours. The reaction mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc) to obtain a crude purified product having ethyl 7-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate as a main component. The crude purified product was recrystallized from ethyl acetate twice to obtain 15.66 g of ethyl 7-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate.

Workup

  1. temperaturecooling
  2. stirringby stirring at the same temperature for 0.5 hours
  3. stirringstirring at 60° C. for 3 hours
  4. extractionThe reaction mixture was extracted with ethyl acetate
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (elution solvent: HEX-EtOAc)
  9. customto obtain a crude
  10. custompurified product
  11. customThe crude purified product
  12. customwas recrystallized from ethyl acetate twice

Sources & evidence

ORD record
ord-52a6c34f8794481f94791125560df3f2
Source dataset
uspto-grants-2015_08
Patent number
US09108977B2

Reaction notes

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