3-Chloro-4-hydroxy-5-methoxybenzaldehyde → 3-(3-Chloro-4-hydroxy-5-methoxy-phenyl)-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-one

HRID 552283Notes

Reaction equation

HRID 552283 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].[Cl:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([O:27][CH3:28])[C:25]=1[OH:26])[CH:21]=O>C(O)C.Cl.C(O)(C)C.O>[Cl:17][C:18]1[CH:19]=[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:23]=[C:24]([O:27][CH3:28])[C:25]=1[OH:26]

Participants

7

Reactant 2

HCID 296223-Chloro-4-hydroxy-5-methoxybenzaldehydeHCID 671661641-(5-Ethyl-4-phenyl-thiophen-2-yl)-ethanone

Product 1

HCID 592489953-(3-Chloro-4-hydroxy-5-methoxy-phenyl)-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-oneYield 59.7%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

A solution of 1-(5-ethyl-4-phenyl-thiophen-2-yl)-ethanone (200 mg, 0.869 mmol) and 3-chloro-4-hydroxy-5-methoxybenzaldehyde (194 mg, 1.04 mmol) in ethanol (2 mL) and 5 N HCl in isopropanol (1 mL) is stirred at rt for 18 h. The dark green solution is diluted with water and extracted with EA. The organic extract is evaporated, dissolved in methanol (5 mL) and THF (5 mL) and treated with Pd/C (150 mg, 10% Pd). The slurry is hydrogenated under 1.8 bar of H2 for 18 h. The mixture is filtered over celite, the solvent is removed in vacuo and the crude product is purified by CC on silica gel eluting with heptane:EA 7:3 to give 3-(3-chloro-4-hydroxy-5-methoxy-phenyl)-1-(5-ethyl-4-phenyl-thiophen-2-yl)-propan-1-one (208 mg) as a colourless oil; LC-MS: tR=1.10 min, [M+1]+=401.12; 1H NMR (CDCl3): δ 7.58 (s, 1H), 7.46-7.30 (m, 5H), 6.83 (d, J=1.8 Hz, 1H), 6.67 (d, J=1.8 Hz, 1H), 3.88 (s, 3H), 3.16 (t, J=7.6 Hz, 2H), 2.98 (t, J=7.6 Hz, 2H), 2.91 (q, J=7.6 Hz, 2H), 1.30 (t, J=7.6 Hz, 3H).

Workup

  1. extractionextracted with EA
  2. extractionThe organic extract
  3. customis evaporated
  4. dissolutiondissolved in methanol (5 mL)
  5. additionTHF (5 mL) and treated with Pd/C (150 mg, 10% Pd)
  6. filtrationThe mixture is filtered over celite
  7. customthe solvent is removed in vacuo
  8. customthe crude product is purified by CC on silica gel eluting with heptane:EA 7:3

Sources & evidence

ORD record
ord-070df507d40d472e9b1ddeb4041c5f96
Source dataset
uspto-grants-2011_05
Patent number
US07951794B2

Reaction notes

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