8-Bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl ester → 8-Allyl-1-ethyl-7-fluoro-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl ester

HRID 477170Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 477170
[CH2:1]([CH:5]([Sn])C=C(CCCC)CCCC)[CH2:2]CC.Br[C:18]1[C:19]([F:38])=[CH:20][CH:21]=[C:22]2[C:26]=1[NH:25][C:24]1[C:27]([CH2:36][CH3:37])([CH2:31][C:32]([O:34][CH3:35])=[O:33])[O:28][CH2:29][CH2:30][C:23]2=1>C1C=CC=CC=1.[Pd].CCOCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:36]([C:27]1([CH2:31][C:32]([O:34][CH3:35])=[O:33])[C:24]2[NH:25][C:26]3[C:22]([C:23]=2[CH2:30][CH2:29][O:28]1)=[CH:21][CH:20]=[C:19]([F:38])[C:18]=3[CH2:5][CH:1]=[CH2:2])[CH3:37]

Komponenten

7

Edukt 2

HCID 147700098-Bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl esterHCID 86589045Tributylallyltin

Produkt 1

HCID 147700108-Allyl-1-ethyl-7-fluoro-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid methyl esterAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23938PalladiumKatalysatorHCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 241BenzeneLösungsmittelHCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

According to the procedure of Kosugi et al, Chem. Letters 301 (1977) tetrakis-(triphenylphosphine) palladium [O] (60 mg) was added to a mixture of tributylallyltin (1.75 g, 0.0053 mol) and 8-bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl ester (1.6 g, 0.0043 mol) in benzene (4.0 mL) under N2. The sealed tube was then heated to 80° C. for 15 hours, more palladium catalyst was added (30 mg), and heating continued for 42 hours at 110°-120° C. The cooled reaction mixture was diluted with Et2O, then filtered through a glass wool plug. The ether was washed twice with brine, then dried (MgSO4) to yield an oil that was purified via flash chromatography. Using 1:7 EtOAc:hexane to afford 1.12 g, (~78%) of 1-ethyl-7-fluoro-1,3,4,9-tetrahydro-8-(2-propenyl)-pyrano[3,4-b]indole-1-acetic acid, methyl ester as a colorless oil. The oil was dissolved in ethanol (40 mL) and 1N sodium hydroxide added (15 mL). The mixture was heated to reflux for 2 hours then cooled and concentrated. 1N HCl was added and the aqueous solution extracted with ether. The ether layers were washed (brine), dried (MgSO4) and concentrated to yield a foamy oil. This was purified by flash chromatography on SiO2 -pretreated with 2% H3PO4 -MeOH. Using 1:2 EtOAc:hexane to give 1 g (73%) of 1-ethyl-7-fluoro-1,3,4,9-tetrahydro-8-(2-propenyl)-pyrano[3,4-b]indole-1-acetic acid as a colorless oil which crystallized from toluene:petroleum ether, m.p. 123°-125° C.

Aufarbeitung

  1. temperatureheating
  2. customThe cooled reaction mixture
  3. filtrationfiltered through a glass wool plug
  4. washThe ether was washed twice with brine
  5. dry with materialdried (MgSO4)
  6. customto yield an oil that
  7. customwas purified via flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-49760c36eb8e449ebe9826fc2760e502
Quelldatensatz
uspto-grants-1989_12
Patentnummer
US04886886

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