Methyl iodide → 5-Chloro-3-hydroxy-3-methyl-6-(piperidin-1-yl)-2,3-dihydrobenzofuran

HRID 637673Notes

Reaction equation

HRID 637673 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:4][C:5]2[O:9][CH2:8][C:7](=[O:10])[C:6]=2[CH:11]=1.[Mg].[CH3:19]I>CCOCC>[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:4][C:5]2[O:9][CH2:8][C:7]([OH:10])([CH3:19])[C:6]=2[CH:11]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 5462224MagnesiumHCID 202556645-chloro-6-(piperidin-1-yl)-benzofuran-3(2H)-one

Product 1

HCID 202556555-Chloro-3-hydroxy-3-methyl-6-(piperidin-1-yl)-2,3-dihydrobenzofuran

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 5.03 g (20.0 mmole) of crude 5-chloro-6-(piperidin-1-yl)-benzofuran-3(2H)-one in 30 ml of absolute ether is added dropwise at room temperature to a freshly prepared Grignard solution of 750 mg (30.8 mmole) of magnesium filings and 4.0 g (28.2 mmole) of methyl iodide in 30 ml of absolute ether. The whole is subsequently boiled under reflux for 45 minutes and poured onto ice/ammonium chloride. The ether phase is separated off and the aqueous phase is extracted twice more with ether. The organic phases are washed with water, combined, dried over sodium sulphate and concentrated in a vacuum rotary evaporator. Chromatography over silica gel with chloroform/ethyl acetate (10:1) yields 5-chloro-3-hydroxy-3-methyl-6-(piperidin-1-yl)-2,3-dihydrobenzofuran in the form of an oil having an Rf of 0.24 [silica gel, chloroform/ethyl acetate (10:1)].

Workup

  1. temperatureunder reflux for 45 minutes
  2. additionpoured onto ice/ammonium chloride
  3. customThe ether phase is separated off
  4. extractionthe aqueous phase is extracted twice more with ether
  5. washThe organic phases are washed with water
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated in a vacuum rotary evaporator

Sources & evidence

ORD record
ord-2750532e34bc433ea5ae5293d6189083
Source dataset
uspto-grants-1985_12
Patent number
US04558043

Reaction notes

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