Sodium Carbonate → 5'-(3-Cyano-5-fluorophenyl)-spiro [cyclopentane-1,3'-[3H]indol]-2'(1'H)-one

HRID 9320

Reaktionsgleichung

Reaktionsgleichung von HRID 9320
[C:1]([C:3]1[CH:4]=[C:5](Br)[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2].[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]2([CH:23](B(O)O)[CH2:22][CH2:21][CH2:20]2)[C:12]1=[O:27].C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>COCCOC.O>[C:1]([C:3]1[CH:4]=[C:5]([C:16]2[CH:15]=[C:14]3[C:19](=[CH:18][CH:17]=2)[NH:11][C:12](=[O:27])[C:13]23[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:6]=[C:7]([F:9])[CH:8]=1)#[N:2]

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27833303-Bromo-5-fluorobenzonitrileHCID 21986244(spiro[cyclopentane-1,3'-[3H]indol]-2'(1'H)-one-5-yl)boronic acid

Produkt 1

HCID 219862605'-(3-Cyano-5-fluorophenyl)-spiro [cyclopentane-1,3'-[3H]indol]-2'(1'H)-oneAusbeute 44 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A solution of 3-cyano-5-fluoro-bromobenzene (0.5 g, 2.6 mmol), and tetrakis (triphenylphosphine)palladium(0) (0.2 g) in ethylene glycol dimethyl ether (20 cm3) was stirred under N2 for 20 minutes. To this mixture was then added (spiro[cyclopentane-1,3′-[3H]indol]-2′(1′H)-one-5-yl)boronic acid (0.9 g, 3.9 mmol) and sodium carbonate (0.8 g, 7.8 mmol) in water (5 cm3). The solution was brought to reflux for 18 hours and then cooled to room temperature, poured into 2N NaOH and extracted with EtOAc (×3). The combined extracts were washed with water, brine, dried (MgSO4), and evaporated. The residue was purified by column chromatography (SiO2, EtOAc, hexane) to afford the subtitled compound (0.35 g, 44%) as white needles. mp: 235–237° C.; 1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.1 (s, 1H), 8.0 (dt, 1H, J=1.7, 2.0, 7.0 Hz), 7.8–7.7 (m, 2H), 7.6 (dd, 1H, J=1.8, 6.4 Hz), 6.9 (d, 1H, J=8.1 Hz), 2.0–1.9 (m, 8H); MS (EI) M+ @ m/z 306.

Aufarbeitung

  1. temperatureto reflux for 18 hours
  2. extractionextracted with EtOAc (×3)
  3. washThe combined extracts were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography (SiO2, EtOAc, hexane)

Quellen und Nachweise

ORD-Eintrag
ord-00d03b2c1c3b4c2a908a9d526535d5cd
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07091234B2

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