3,5-Dimethyl-4-hydroxybenzaldehyde → 1-(5-Ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-one

HRID 552293Notes

Reaction equation

HRID 552293 reaction equation
[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:10])[CH3:9])=[CH:5][C:4]=1[C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)[CH3:2].[CH3:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([CH3:28])[C:26]=1[OH:27])[CH:22]=O>C(O)C.Cl.C(O)(C)C.O>[CH2:1]([C:3]1[S:7][C:6]([C:8](=[O:10])[CH2:9][CH2:22][C:21]2[CH:24]=[C:25]([CH3:28])[C:26]([OH:27])=[C:19]([CH3:18])[CH:20]=2)=[CH:5][C:4]=1[C:11]1[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=1)[CH3:2]

Participants

7

Reactant 2

HCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 671663071-(5-Ethyl-4-p-tolyl-thiophen-2-yl)-ethanone

Product 1

HCID 592489921-(5-Ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-oneYield 105.7%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A solution of 1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-ethanone (28 mg, 0.115 mmol) and 3,5-dimethyl-4-hydroxybenzaldehyde (26 mg, 0.172 mmol) in ethanol (1.5 mL) and 5 N HCl in isopropanol (0.3 mL) is stirred at rt for 18 h. The solution is diluted with water and extracted with EA. The organic extract is evaporated, dissolved in methanol (3 mL) and THF (3 mL) and treated with Pd/C (30 mg, 10% Pd). The slurry is stirred under 1.5 bar of H2 for 18 h. The mixture is filtered, the solvent of the filtrate is removed in vacuo and the crude product is purified by prep. HPLC to give 1-(5-ethyl-4-p-tolyl-thiophen-2-yl)-3-(4-hydroxy-3,5-dimethyl-phenyl)-propan-1-one (46 mg) as a colourless oil; LC-MS: tR=1.13 min, [M+1]+=379.22.

Workup

  1. extractionextracted with EA
  2. extractionThe organic extract
  3. customis evaporated
  4. dissolutiondissolved in methanol (3 mL)
  5. additionTHF (3 mL) and treated with Pd/C (30 mg, 10% Pd)
  6. filtrationThe mixture is filtered
  7. customthe solvent of the filtrate is removed in vacuo
  8. customthe crude product is purified by prep

Sources & evidence

ORD record
ord-aad9c69b0d7b4d698e683df1e79cc9c3
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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