Triphenylphosphine → 5-Ethoxycarbonylmethylene-7-fluoro-1-oxo-1,3,4,5-tetrahydro-azepino[3,4-b]indole-2,10-dicarboxylic acid di-tert-butyl ester

HRID 2234771Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2234771
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([O:24][C:25]([N:27]1[C:35]2[C:30](=[CH:31][C:32]([F:36])=[CH:33][CH:34]=2)[C:29](I)=[C:28]1[C:38]([N:40]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:41][CH2:42][CH:43]=[CH:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])=[O:39])=[O:26])([CH3:23])([CH3:22])[CH3:21]>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:53]([O:52][C:50]([N:40]1[CH2:41][CH2:42][C:43](=[CH:44][C:45]([O:47][CH2:48][CH3:49])=[O:46])[C:29]2[C:30]3[C:35](=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)[N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[C:28]=2[C:38]1=[O:39])=[O:51])([CH3:55])([CH3:56])[CH3:54]

Komponenten

5

Edukt 2

HCID 11776TriphenylphosphineHCID 686374172-[Tert-butoxycarbonyl-(4-ethoxycarbonyl-but-3-enyl)-aminocarbonyl]-5-fluoro-3-iodo-indole-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 686390865-Ethoxycarbonylmethylene-7-fluoro-1-oxo-1,3,4,5-tetrahydro-azepino[3,4-b]indole-2,10-dicarboxylic acid di-tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A suspension of triphenylphosphine (3.36 g, 12.8 mmol), Pd(OAc)2 (1.44 g, 6.40 mmol) and Ag2CO3 (3.53 g, 12.8 mmol) in anhydrous THF (100 mL) is stirred at room temperature for 15 minutes. A solution of 2-[tert-butoxycarbonyl-(4-ethoxycarbonyl-but-3-enyl)-aminocarbonyl]-5-fluoro-3-iodo-indole-1-carboxylic acid tert-butyl ester (4.03 g, 6.40 mmol), prepared as in reference 15, in THF (10 mL) is added to the above prepared suspension. The mixture is heated at 60° C. for 16 hours. The inorganic precipitate is removed and the organic layer is concentrated. The residue is purified by silica gel column chromatography and eluted with EtOAc-Hexanes to give the 5-ethoxycarbonylmethylene-7-fluoro-1-oxo-1,3,4,5-tetrahydro-azepino[3,4-b]indole-2,10-dicarboxylic acid di-tert-butyl ester; 1H NMR (CDCl3) δ 1.34 (t, 3H, J=7.6 Hz), 1.57 (s, 9H), 1.60 (s, 9H), 3.46-3.52 (m, 2H), 4.13 (t, 2H, J=4.8 Hz), 4.24 (q, 2H, J=7.6 Hz), 6.30 (t, 1H, J=2.8 Hz), 7.21 (td, 1H, J1=2.8 Hz, J2=9.2 Hz), 7.42 (dd, 1H, J1=2.8 Hz, J2=8.8 Hz), 8.10 (dd, 1H, J1=4.0 Hz, J2=9.2 Hz); m/z [M++Na] 525.0.

Aufarbeitung

  1. temperatureThe mixture is heated at 60° C. for 16 hours
  2. customThe inorganic precipitate is removed
  3. concentrationthe organic layer is concentrated
  4. customThe residue is purified by silica gel column chromatography
  5. washeluted with EtOAc-Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-62519ecf8a9e474398757aeb120112dd
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07713958B2

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