Chlorosuccinimide → 8-amino-5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran

HRID 440688Notes

Reaction equation

HRID 440688 reaction equation
[NH2:1][C:2]1[C:11]2[O:10][CH2:9][CH2:8][CH2:7][C:6]=2[CH:5]=[CH:4][C:3]=1[F:12].[Cl:13]N1C(=O)CCC1=O.[Cl-].[Li+]>CN(C)C=O>[NH2:1][C:2]1[C:11]2[O:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]([Cl:13])=[CH:4][C:3]=1[F:12]

Participants

5

Reactant 3

HCID 31398ChlorosuccinimideHCID 433294Lithium ChlorideHCID 224047958-amino-3,4-dihydro-7-fluoro-2H-1-benzopyran

Product 1

HCID 224047928-amino-5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyranYield 49.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 3.7 grams (0.022 mole) of 8-amino-3,4-dihydro-7-fluoro-2H-1-benzopyran in 50 mL of N,N-dimethylformamide was added dropwise a solution of 3.0 grams (0.022 mole) of N-chlorosuccinimide in about 20 mL of N,N-dimethylformamide. Upon completion of the addition, the reaction mixture was stirred for about 90 minutes and poured into an aqueous 10% lithium chloride solution. The mixture was extracted with diethyl ether. An insoluble material was collected by filtration and dissolved in methylene chloride. The methylene chloride solution was washed with water and dried with magnesium sulfate. The mixture was filtered, and the filtrate was set aside. The diethyl ether extract was washed with an aqueous 10% lithium chloride solution and dried with magnesium sulfate. The mixture was filtered, and the filtrate was combined with the methylene chloride filtrate. The combination was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel with 1:4 ethyl acetate:hexane as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.2 grams of 8-amino-5-chloro-3,4-dihydro-7-fluoro-2H-1-benzopyran. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of the addition
  2. extractionThe mixture was extracted with diethyl ether
  3. filtrationAn insoluble material was collected by filtration
  4. dissolutiondissolved in methylene chloride
  5. washThe methylene chloride solution was washed with water
  6. dry with materialdried with magnesium sulfate
  7. filtrationThe mixture was filtered
  8. extractionThe diethyl ether extract
  9. washwas washed with an aqueous 10% lithium chloride solution
  10. dry with materialdried with magnesium sulfate
  11. filtrationThe mixture was filtered
  12. concentrationThe combination was concentrated under reduced pressure to a residue, which
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-53d11da8b1914ab08060d6d4b6f5d874
Source dataset
uspto-grants-1996_05
Patent number
US05521147

Reaction notes

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