Sodium Iodide → 5-acetoxymethoxy-7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepine

HRID 1184653Notes

Reaction equation

HRID 1184653 reaction equation
[Cl:1][C:2]1[CH:35]=[CH:34][C:5]2[N:6]([C:15](=[O:33])[C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:31])[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[CH3:30])=[CH:18][C:17]=3[CH3:32])[CH2:7][CH2:8][CH2:9][CH:10]([O:11][CH2:12]SC)[C:4]=2[CH:3]=1.S(Cl)(Cl)(=O)=O.[C:41]([O-:44])(=[O:43])[CH3:42].[Na+].[I-].[Na+]>ClCCCl.C(OCC)(=O)C.C(#N)C>[C:41]([O:44][CH2:12][O:11][CH:10]1[CH2:9][CH2:8][CH2:7][N:6]([C:15](=[O:33])[C:16]2[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:31])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH3:30])=[CH:18][C:17]=2[CH3:32])[C:5]2[CH:34]=[CH:35][C:2]([Cl:1])=[CH:3][C:4]1=2)(=[O:43])[CH3:42]

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 24648Sulfuryl chlorideHCID 517045Sodium AcetateHCID 251342157-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine

Product 1

HCID 667329195-acetoxymethoxy-7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepineYield 53.7%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

7-Chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-5-methylthiomethoxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine (509 mg, 1.0 mmol) was dissolved in 1,2-dichloroethane (10 ml). Sulfuric chloride (0.12 ml, 1.5 mmol) was added thereto, and the mixture was stirred at room temperature for 15 minutes. The obtained mixture was concentrated under reduced pressure, and acetonitrile (10 ml), sodium acetate (246 mg, 2.0 mmol), and sodium iodide (450 mg, 3.0 mmol) were added to the residue, and then the mixture was heated under reflux for 1 hour. After cooling to room temperature, ethyl acetate was added thereto, and the insoluble subject was removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=65:35→50:50). The purified product was concentrated under reduced pressure, and the residue was dissolved in aqueous acetonitrile. After concentration at room temperature under reduced pressure, the resulted precipitates were collected by filtration, and dried to obtain 280 mg of 5-acetoxymethoxy-7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepine as white powder.

Workup

  1. additionwere added to the residue
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 1 hour
  4. temperatureAfter cooling to room temperature
  5. customwas removed by filtration
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=65:35→50:50)
  8. concentrationThe purified product was concentrated under reduced pressure
  9. dissolutionthe residue was dissolved in aqueous acetonitrile
  10. concentrationAfter concentration at room temperature under reduced pressure
  11. customthe resulted precipitates
  12. filtrationwere collected by filtration
  13. customdried

Sources & evidence

ORD record
ord-9c4d97df4d2b492f88b9a1e1a75ae9cd
Source dataset
uspto-grants-2014_03
Patent number
US08669229B2

Reaction notes

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