Sodium hydride → 1-(4-Hydroxy-3-methylphenyl)-3-(3-methylbenzothiophen-2-yl)propan-1-one

HRID 241359Notes

Reaction equation

HRID 241359 reaction equation
[H-].[Na+].C([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:24])[CH2:18][C:19](OCC)=O)=[CH:13][C:12]=1[CH3:25])C1C=CC=CC=1.ClC[C:28]1[S:29][C:30]2[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=2[C:32]=1[CH3:33]>C1COCC1>[OH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](=[O:24])[CH2:18][CH2:19][C:28]2[S:29][C:30]3[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=3[C:32]=2[CH3:33])=[CH:13][C:12]=1[CH3:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 12993426Ethyl 3-(4-benzyloxy-3-methylphenyl)-3-oxopropionateHCID 132472182-(Chloromethyl)-3-methylbenzo[b]thiophene

Product 1

HCID 668845751-(4-Hydroxy-3-methylphenyl)-3-(3-methylbenzothiophen-2-yl)propan-1-oneYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Then, to a suspension of 55% sodium hydride (123 mg, 3.07 mmol) in THF (18 mL) was added dropwise over 10 minutes under N2 atmosphere, a solution of ethyl 3-(4-benzyloxy-3-methylphenyl)-3-oxopropionate (870 mg, 2.79 mmol) in THF (5 mL). After 20 minutes, to the resultant mixture was added dropwise over 10 minutes a solution of 2-chloromethyl-3-methylbenzothiophene (548 mg, 2.79 mmol) in THF (5 mL). The mixture was heated under reflux for 25 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was heated in acetic acid (18 mL) and concentrated hydrochloric acid (4 mL) at 110° C. for 20 hours. The reaction mixture was cooled at room temperature, extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate solution, and saturated brine, successively. After drying over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1), to give the titled compound as a yellow crystal (790 mg, yield 95%).

Workup

  1. additionwas added dropwise over 10 minutes under N2 atmosphere
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 25 hours
  4. concentrationconcentrated under reduced pressure
  5. temperatureThe residue was heated in acetic acid (18 mL)
  6. waitconcentrated hydrochloric acid (4 mL) at 110° C. for 20 hours
  7. temperatureThe reaction mixture was cooled at room temperature
  8. extractionextracted with ethyl acetate
  9. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate solution, and saturated brine
  10. dry with materialAfter drying over anhydrous sodium sulfate
  11. customthe solvent was removed under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-59343d1f1c7c4d10a695a697ce54ad4e
Source dataset
uspto-grants-2014_02
Patent number
US08648208B2

Reaction notes

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