3,5-Dimethyl-4-hydroxybenzaldehyde → 3-(4-Hydroxy-3,5-dimethyl-phenyl)-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-one

HRID 552278

Reaction equation

HRID 552278 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][CH:14]=[CH:13][CH:12]=1)[CH3:2].[CH3:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([CH3:27])[C:25]=1[OH:26])[CH:21]=O>C(O)C.Cl.C(O)(C)C.O>[OH:26][C:25]1[C:24]([CH3:27])=[CH:23][C:20]([CH2:21][CH2:9][C:8]([C:6]2[S:7][C:3]([CH2:1][CH3:2])=[C:4]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:5]=2)=[O:10])=[CH:19][C:18]=1[CH3:17]

Participants

7

Reactant 2

HCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 671661641-(5-Ethyl-4-phenyl-thiophen-2-yl)-ethanone

Product 1

HCID 592489883-(4-Hydroxy-3,5-dimethyl-phenyl)-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-oneYield 58.2%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A solution of 1-(5-ethyl-4-phenyl-thiophen-2-yl)-ethanone (64 mg, 0.278 mmol) and 3,5-dimethyl-4-hydroxybenzaldehyde (53 mg, 0.334 mmol) in ethanol (1.2 mL) and 5 N HCl in isopropanol (0.6 mL) is stirred at rt for 1 h. The dark green solution is diluted with water and extracted with EA. The organic extract is evaporated, dissolved in methanol (1 mL) and THF (1 mL), and treated with Pd/C (60 mg, 10% Pd). The slurry is hydrogenated under 1.4 bar of H2 for 1.5 h. The mixture is filtered over celite, the solvent is removed in vacuo and the crude product is purified on prep. TLC plates with heptane:EA 2:1 to give 3-(4-hydroxy-3,5-dimethyl-phenyl)-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-one (59 mg) as a yellow oil; LC-MS: tR=1.11 min; 1H NMR (CDCl3): δ 7.58 (s, 1H), 7.46-7.30 (m, 5H), 6.85 (s, 2H), 4.56 (s, 1H), 3.18-3.10 (m, 2H), 2.97-2.86 (m, 4H), 2.22 (s, 6H), 1.30 (t, J=7.6 Hz, 3H).

Workup

  1. extractionextracted with EA
  2. extractionThe organic extract
  3. customis evaporated
  4. dissolutiondissolved in methanol (1 mL)
  5. additionTHF (1 mL), and treated with Pd/C (60 mg, 10% Pd)
  6. filtrationThe mixture is filtered over celite
  7. customthe solvent is removed in vacuo
  8. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-f9f4bea4cd2141c78ebf498dcad1bca1
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Linked notes

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