Iodine → 1-(Benzo[b]thiophen-4-yl)-2-cyclopropylethan-1-one

HRID 2183678Notes

Reaction equation

HRID 2183678 reaction equation
Br[C:2]1[C:10]2[CH:9]=[CH:8][S:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Mg].II.CON(C)[C:17](=[O:22])[CH2:18][CH:19]1[CH2:21][CH2:20]1>O1CCCC1>[S:7]1[CH:8]=[CH:9][C:10]2[C:2]([C:17](=[O:22])[CH2:18][CH:19]3[CH2:21][CH2:20]3)=[CH:3][CH:4]=[CH:5][C:6]1=2

Participants

6

Reactant 4

HCID 807IodineHCID 5462224MagnesiumHCID 120942084-Bromobenzo[b]thiophene2×HCID 224737662-cyclopropyl-N-methoxy-N-methylacetamide

Product 1

HCID 224741351-(Benzo[b]thiophen-4-yl)-2-cyclopropylethan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A few drops of a solution of 4-bromobenzo[b]thiophene (2.84 g; prepared in a manner similar to that described in Example 9 Method A) in tetrahydrofuran (20 ml) was added under nitrogen to magnesium turnings (0.4 g). Two crystals of iodine were added and heat was applied to initiate the reaction. The remainder of the 4-bromobenzo[b]thiophene solution was added at reflux temperature over 20 minutes, then the mixture was heated under reflux for 2 hours. A solution of N-methoxy-N-methylcyclopropaneacetamide (2.0 g) in tetrahydrofuran (10 ml) was added, the mixture was heated under reflux for 2.5 hours, then it was stirred at ambient temperature for 18 hours and quenched by the addition of 2M hydrochloric acid (40 ml). The mixture was stirred at ambient temperature for 1 hour, then the product was extracted into ethyl acetate (3×30 ml). The combined extracts were washed with water (30 ml) and saturated aqueous sodium chloride solution (20 ml), dried (MgSO4), and the solvents were removed in vacuo. The residue was purified by flash chromatography over silica using petroleum ether (b.p. 60-80° C.) followed by a 95:5 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluants. Appropriate fractions were combined and the solvents removed in vacuo to give 1-(benzo[b]thiophen-4-yl)-2-cyclopropylethan-1-one (1.2 g) as a colourless oil which was used without further purification.

Workup

  1. customprepared in a manner similar to
  2. temperatureheat
  3. customthe reaction
  4. temperatureat reflux temperature over 20 minutes
  5. temperaturethe mixture was heated
  6. temperatureunder reflux for 2 hours
  7. temperaturethe mixture was heated
  8. temperatureunder reflux for 2.5 hours
  9. customquenched by the addition of 2M hydrochloric acid (40 ml)
  10. stirringThe mixture was stirred at ambient temperature for 1 hour
  11. extractionthe product was extracted into ethyl acetate (3×30 ml)
  12. washThe combined extracts were washed with water (30 ml) and saturated aqueous sodium chloride solution (20 ml)
  13. dry with materialdried (MgSO4)
  14. customthe solvents were removed in vacuo
  15. customThe residue was purified by flash chromatography over silica
  16. additionfollowed by a 95:5 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluants
  17. customthe solvents removed in vacuo

Sources & evidence

ORD record
ord-9b8d4789f5b34ffbbf5f6b2ac9fddf24
Source dataset
uspto-grants-2005_05
Patent number
US06900216B2

Reaction notes

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