Pyridine → 4-[3-(8,8-Dimethyl-5-p-tolyl-7,8-dihydro-naphthalen-2-yl)-3-hydroximino-propenyl]-benzoic Acid

HRID 2114083Notes

Reaction equation

HRID 2114083 reaction equation
[CH3:1][C:2]1([CH3:38])[C:11]2[CH:10]=[C:9]([C:12](=O)[CH:13]=[CH:14][C:15]3[CH:29]=[CH:28][C:18]([C:19]([O:21]CC[Si](C)(C)C)=[O:20])=[CH:17][CH:16]=3)[CH:8]=[CH:7][C:6]=2[C:5]([C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=2)=[CH:4][CH2:3]1.Cl.[NH2:40][OH:41].N1C=CC=CC=1.[F-]>CCO.CS(C)=O.O>[CH3:1][C:2]1([CH3:38])[C:11]2[CH:10]=[C:9]([C:12](=[N:40][OH:41])[CH:13]=[CH:14][C:15]3[CH:29]=[CH:28][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=3)[CH:8]=[CH:7][C:6]=2[C:5]([C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=2)=[CH:4][CH2:3]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 28179Fluoride IonHCID 443297Hydroxyamine hydrochlorideHCID 688321412-Trimethylsilanyl-ethyl 4-[3-(8,8-dimethyl-5-p-tolyl-7,8-dihydro-naphthalen-2-yl)-3-oxo-propenyl]-benzoate2×

Product 1

HCID 729541014-[3-(8,8-Dimethyl-5-p-tolyl-7,8-dihydro-naphthalen-2-yl)-3-hydroximino-propenyl]-benzoic AcidYield 42%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 2-trimethylsilanyl-ethyl 4-[3-(8,8-dimethyl-5-p-tolyl-7,8-dihydro-naphthalen-2-yl)-3-oxo-propenyl]-benzoate (Compound 6, 240 mg, 0.46 mmol) in 5 mL of EtOH was added hydroxylamine hydrochloride (64 mg, 0.92 mmol) and pyridine (77 mg, 0.97 mmol). The reaction mixture was then heated at reflux for 6 h. After cooling to room temperature, the solvent was removed in vacuo and the residue was taken up in water. The aqueous layer was adjusted to pH=4-5 with 1 N HCl and extracted with ethyl acetate (3×10 mL). The organic layers were combined and washed with water (2×10 mL) and brine (1×10 mL), dried (MgSO4) and concentrated at reduced pressure to obtain a yellow crude oil. This crude product was then dissolved in 2 mL of dimethylsulfoxide (DMSO) and tetraethylammomium fluoride (TEAF) (137 g, 0.92 mmol) was added. After stirring at room temperature for 0.5 h, the mixture was diluted with water (10 mL), extracted with ethyl acetate (3×5 mL), washed with brine (1×5 mL), dried (MgSO4) and concentrated at reduced pressure. Purification by recrystallization with acetonitrile yielded Substance 7c, (a mixture of E/Z isomers, 84 mg, 42% yield).

Workup

  1. temperatureThe reaction mixture was then heated
  2. temperatureat reflux for 6 h
  3. customthe solvent was removed in vacuo
  4. extractionextracted with ethyl acetate (3×10 mL)
  5. washwashed with water (2×10 mL) and brine (1×10 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated at reduced pressure
  8. customto obtain a yellow crude oil
  9. extractionextracted with ethyl acetate (3×5 mL)
  10. washwashed with brine (1×5 mL)
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated at reduced pressure
  13. customPurification
  14. customby recrystallization with acetonitrile yielded Substance 7c
  15. addition(a mixture of E/Z isomers, 84 mg, 42% yield)

Sources & evidence

ORD record
ord-b2b111101fed41aa8d8a9ce802be1c9a
Source dataset
uspto-grants-2008_10
Patent number
US07432388B2

Reaction notes

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