Methyl iodide → 1'-{[(2S)-1-methyl-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-one

HRID 1965697Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1965697
[O:1]=[C:2]1[NH:6][C@H:5]([CH2:7][N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3([CH2:20][O:19][C:18]4[CH:21]=[C:22]5[C:26](=[CH:27][C:17]3=4)[CH2:25][CH2:24][O:23]5)[C:9]2=[O:28])[CH2:4][CH2:3]1.[H-].[Na+].I[CH3:32]>CN(C)C=O>[CH3:32][N:6]1[C:2](=[O:1])[CH2:3][CH2:4][C@H:5]1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]2([CH2:20][O:19][C:18]3[CH:21]=[C:22]4[C:26](=[CH:27][C:17]2=3)[CH2:25][CH2:24][O:23]4)[C:9]1=[O:28]

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 593520751'-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-one

Produkt 1

HCID 593521491'-{[(2S)-1-methyl-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-oneAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 1′-{[(2S)-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.235 g, 0.623 mmol) in dry N,N-dimethylformamide (10 mL) was added sodium hydride (60% in mineral oil, 0.04 g, 1.04 mmol) at ambient temperature. The mixture was stirred for 15 min, and iodomethane (0.28 g, 2.0 mmol) was added in one portion. The reaction mixture was stirred at ambient temperature for 1 h, and concentrated to dryness. The residue was purified by flash chromatography (hexanes/ethyl acetate; gradient 0% to 30%) to afford 1′-{[(2S)-1-methyl-5-oxopyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1H)-one (0.15 g, 62%) as colorless solid: mp 72-76° C.; 1H NMR (300 MHz, CDCl3) δ7.33 (dd, J=7.5, 7.5 Hz, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.09 (dd, J=7.5, 7.5 Hz, 1H), 6.91 (d, J=7.5 Hz, 1H), 6.46-6.38 (m, 2H), 4.77 (ABq, 2H), 4.53 (t, J=8.6 Hz, 2H), 4.03-3.75 (m, 3H), 3.11-2.83 (m, 5H), 2.61-2.42 (m, 1H), 2.42-2.27 (m, 1H), 2.26-2.07 (m, 1H), 2.03-1.84 (m, 1H); 13C NMR (75 MHz, CDCl3) δ178.4, 178.4, 175.1, 175.0, 161.8, 161.3, 161.2, 142.1, 141.9, 132.5, 132.4, 128.9 (2C), 124.3, 124.2, 123.7 (2C), 120.0, 119.9, 119.7, 119.6, 118.6, 118.5, 108.0, 93.2, 80.5, 72.3, 58.1, 58.0, 57.5 (2C), 43.0, 42.9, 29.3, 29.2, 28.9, 28.7 (2C), 22.6 (2C); MS (ES+) m/z 391.1 (M+1).

Aufarbeitung

  1. stirringThe reaction mixture was stirred at ambient temperature for 1 h
  2. concentrationconcentrated to dryness
  3. customThe residue was purified by flash chromatography (hexanes/ethyl acetate; gradient 0% to 30%)

Quellen und Nachweise

ORD-Eintrag
ord-f1a5738015ac49018366005f77968788
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415370B2

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