1-(diphenylmethyl)-1H-indole-2,3-dione → 1-(diphenylmethyl)-3-hydroxy-3-(7-hydroxy-3,4-dihydro-2H-chromen-6-yl)-1,3-dihydro-2H-indol-2-one

HRID 1407397Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1407397
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([OH:11])[CH:9]=2)[CH2:4][CH2:3][CH2:2]1.C([Mg]Cl)(C)C.[C:17]1([CH:23]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26](=[O:33])[C:25]2=[O:34])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCCC1.ClCCl.[Cl-].[NH4+]>[C:35]1([CH:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]([OH:33])([C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][C:8]=3[OH:11])[O:1][CH2:2][CH2:3][CH2:4]4)[C:25]2=[O:34])[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Komponenten

7

Edukt 3

HCID 19692771-(diphenylmethyl)-1H-indole-2,3-dioneHCID 12236542Chroman-7-olHCID 178418918HCID 178418918, Verbindung

Produkt 1

HCID 685970791-(diphenylmethyl)-3-hydroxy-3-(7-hydroxy-3,4-dihydro-2H-chromen-6-yl)-1,3-dihydro-2H-indol-2-oneAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a cooled (0° C.) solution of chroman-7-ol (Cube, R. V., et al., Bioorg. Med. Chem. Lett. (2005), 15(9):2389-93) (0.55 g, 3.66 mmol) in tetrahydrofuran (11 mL) under nitrogen was added isopropylmagnesium chloride (2.4 mL, 2 M in tetrahydrofuran, 4.8 mmol). The resulting solution was stirred at 0° C. for 30 min. A suspension of 1-(diphenylmethyl)indoline-2,3-dione (1.16 g, 3.70 mmol) in dichloromethane (4 mL) was added. The reaction was stirred at 0° C. for 10 min, then warmed to ambient temperature and stirred for 15.5 h. The reaction was diluted with saturated ammonium chloride solution (10 mL) and the organic solvents were removed under reduced pressure. The residual mixture was diluted with water (50 mL) and extracted with ethyl acetate (3×25 mL). The combined organic solution was washed with brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography with hexanes/ethyl acetate (7:3) to afford 1-(diphenylmethyl)-3-hydroxy-3-(7-hydroxy-3,4-dihydro-2H-chromen-6-yl)-1,3-dihydro-2H-indol-2-one (1.37 g, 81%) as a light yellow solid: mp 204-206° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) δ8.90 (s, 1H), 7.49 (dd, J=5.6, 3.2 Hz, 1H), 7.38-7.23 (m, 10H), 7.12-7.06 (m, 2H), 6.95 (s, 1H), 6.52-6.47 (m, 3H), 4.23 (s, 1H), 4.121 (dd, J=5.7, 4.5 Hz, 2H), 2.53 (t, J=6.3 Hz, 2H), 1.95-1.87 (m, 2H); MS (ES+) m/z 486.1 (M+23).

Aufarbeitung

  1. additionwas added
  2. stirringThe reaction was stirred at 0° C. for 10 min
  3. temperaturewarmed to ambient temperature
  4. stirringstirred for 15.5 h
  5. customthe organic solvents were removed under reduced pressure
  6. additionThe residual mixture was diluted with water (50 mL)
  7. extractionextracted with ethyl acetate (3×25 mL)
  8. washThe combined organic solution was washed with brine (50 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash column chromatography with hexanes/ethyl acetate (7:3)

Quellen und Nachweise

ORD-Eintrag
ord-aae0dd956301486b97a33b99bcce94c2
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08916580B2

Notizen zur Reaktion

Wird geladen…