Ethyl Acetate → (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(4-methoxytetrahydropyran-4-yl)-phenyl]pent-4-enoic acid methyl ester

HRID 1360083

Reaktionsgleichung

Reaktionsgleichung von HRID 1360083
[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9](=[O:18])[C:10]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])[CH2:5][CH:6]=[CH2:7].I[C:21]1[CH:26]=[CH:25][C:24]([C:27]2([O:33][CH3:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9](=[O:18])[C:10]1[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:5]/[CH:6]=[CH:7]/[C:21]1[CH:22]=[CH:23][C:24]([C:27]2([O:33][CH3:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[CH:25][CH:26]=1

Komponenten

8

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 57762532tetrahydro-4-(4-iodophenyl)-4-methoxy-2H-pyranHCID 57762562(S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester

Produkt 1

HCID 57762529(S,E)-2-(2,6-dichlorobenzamido)-5-[4-(4-methoxytetrahydropyran-4-yl)-phenyl]pent-4-enoic acid methyl esterAusbeute 79,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 80271Tri-o-tolylphosphineKatalysatorHCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Under an argon atmosphere, palladium acetate (295 mg) and tris(2-methylphenyl)phosphine (384 mg) were added to a suspension of (S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (7.60 g), tetrahydro-4-(4-iodophenyl)-4-methoxy-2H-pyran (8.00 g) and potassium carbonate (5.21 g) in DMF (90 ml), and the resulting mixture was stirred at 80° C. for 2 hours. After cooling the reaction solution to room temperature, ethyl acetate was added thereto, and the resulting mixture was washed 3 times with water and once with saturated brine, followed by drying the organic layer over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluent:cyclohexane/chloroform=2/1→1/4). The obtained crudely purified product was further purified by column chromatography (silica gel, eluent:cyclohexane/ethyl acetate=4/1) to obtain (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(4-methoxytetrahydropyran-4-yl)-phenyl]pent-4-enoic acid methyl ester (9.80 g).

Aufarbeitung

  1. temperatureAfter cooling the reaction solution to room temperature
  2. washthe resulting mixture was washed 3 times with water
  3. dry with materialby drying the organic layer over anhydrous sodium sulfate
  4. customAfter removing anhydrous sodium sulfate
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by column chromatography (silica gel, eluent:cyclohexane/chloroform=2/1→1/4)
  8. customThe obtained crudely purified product
  9. customwas further purified by column chromatography (silica gel, eluent:cyclohexane/ethyl acetate=4/1)

Quellen und Nachweise

ORD-Eintrag
ord-c5fd469bd67c4ee4a6585030b0bb575e
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07879837B2

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