Sulfuric Acid → HCID 22998295, compound

HRID 1166428Notes

Reaction equation

HRID 1166428 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[NH:6][C:7]3[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][C:8]=3[CH2:9][CH2:10][C:4]=2[CH:3]=1.C(N(CC)CC)C.[Cl:25][CH2:26][CH2:27][C:28](Cl)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O>C1(C)C=CC=CC=1.O1CCCC1>[Br:15][C:12]1[CH:13]=[CH:14][C:7]2[N:6]([CH2:28][CH2:27][CH2:26][Cl:25])[C:5]3[CH:16]=[CH:17][C:2]([Br:1])=[CH:3][C:4]=3[CH2:10][CH2:9][C:8]=2[CH:11]=1

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 8471TriethylamineHCID 693643-Chloropropionyl chlorideHCID 640268HCID 640268, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 22998295HCID 22998295, compoundYield 87.9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

2,8-Dibromo-10,11-dihydro-5H-dibenz[b,f]azepine (1.41 g. 4.0 mmol, prepared according to K. Smith et al., Tetrahedron, 48, 7479 (1992)), was dissolved in toluene (25 ml). Triethylamine (0.60 ml, 4.4 mmol) and 3-chloropropionyl chloride (0.50 ml, 5.2 mmol) were added to thee stirred solution at room temperature. Stirring was continued at room temperature for 1 h and at reflux temperature for 2.5 h. The reaction mixture was cooled, filtered and evaporated in vacuo. The crude 3-chloro-1-(2,8-dibromo-10,11-dihydro-5H-dibenz[b,f]-azepine-5-yl)propan-1-one was used in the next step without further purification. A solution of lithium aluminium hydride (0.326 g, 8.56 mmol) in dry tetrahydrofuran (30 ml) was cooled in an ice bath and concentrated sulphuric acid (0.428 g, 4.28 mmol) was added dropwise. The solution was stirred at room temperature for 0.5 h. A solution of the above product (1.90 g, 4.28 mmol) was added dropwise and stirring was continued for 0.5 h. The reaction was then quenched by careful addition of ethyl acetate (5 ml) followed by water (0.8 ml). Filtration of the mixture and evaporation of the filtrate in vacuo afforded 1.51 g (82%) 2,8-dibromo-5-(3-chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepine as a foam, which was used in the next step without further purification.

Workup

  1. stirringStirring
  2. temperatureat reflux temperature for 2.5 h
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude 3-chloro-1-(2,8-dibromo-10,11-dihydro-5H-dibenz[b,f]-azepine-5-yl)propan-1-one was used in the next step without further purification
  7. stirringThe solution was stirred at room temperature for 0.5 h
  8. stirringstirring
  9. waitwas continued for 0.5 h
  10. customThe reaction was then quenched by careful addition of ethyl acetate (5 ml)
  11. filtrationFiltration of the mixture and evaporation of the filtrate in vacuo

Sources & evidence

ORD record
ord-77cae6ec09674751940c899e6007d283
Source dataset
uspto-grants-2003_09
Patent number
US06613791B1

Reaction notes

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