Sodium hydride → 3,4-dihydro-6-[(1,3-dioxolan-2-yl)methoxy]-3-(1-phenylmethyl-4-piperidinyl)-2(1H)-quinazolinone

HRID 2217270Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2217270
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[N:8]([CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:17][CH2:16]1)[CH2:7]2.Br[CH2:29][CH:30]1[O:34][CH2:33][CH2:32][O:31]1.[K+].[Br-]>CN(C)C=O>[O:31]1[CH2:32][CH2:33][O:34][CH:30]1[CH2:29][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[N:8]([CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH2:17][CH2:16]1)[CH2:7]2

Komponenten

6

Edukt 4

HCID 24758Sodium hydrideHCID 780681,3-Dioxolane, 2-(bromomethyl)-HCID 253877Potassium BromideHCID 179586923,4-dihydro-6-hydroxy-3-(1-phenylmethyl-4-piperidinyl)-2(1H)-quinazolinone

Produkt 1

HCID 693081203,4-dihydro-6-[(1,3-dioxolan-2-yl)methoxy]-3-(1-phenylmethyl-4-piperidinyl)-2(1H)-quinazolinone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

0.36 g (14.25 mmol) of 95% sodium hydride was added batchwise, with stirring, to a solution of 5.0 g (14.82 mmol) of 3,4-dihydro-6-hydroxy-3-(1-phenylmethyl-4-piperidinyl)-2(1H)-quinazolinone in 120 mL of anhydrous dimethylformamide at ambient temperature and the mixture was then kept for 15 minutes at 50° C. A thick, colorless slurry was formed. After the addition of 5.0 g (37.04 mmol) of 2-(bromomethyl)-1,3-dioxolane the mixture was heated to 90° C. for 90 minutes. After cooling, the mixture was stirred into saturated aqueous saline solution and extracted exhaustively with ethyl acetate. The combined extracts were dried over sodium sulfate and evaporated down in vacuo, the residue remaining was purified by column chromatography on silica gel (30-60 μm) using dichloromethane/EE/cyclohexane/methanol/concentrated ammonia 60/16/5/5/0.6 v/v/v/v/v as eluant. Working up the corresponding fractions yielded 2.5 g (41% of theoretical) of a colorless oil, Rf=0.47 (dichloromethane/EE/cyclohexane/methanol/concentrated ammonia 60/16/5/5/0.6 v/v/v/v/v). IR (KBr): 1662 (C═O) cm−1.

Aufarbeitung

  1. customA thick, colorless slurry was formed
  2. temperatureAfter cooling
  3. extractionextracted exhaustively with ethyl acetate
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. customevaporated down in vacuo
  6. customthe residue remaining was purified by column chromatography on silica gel (30-60 μm)
  7. customWorking up the corresponding fractions yielded 2.5 g (41% of theoretical) of a colorless oil, Rf=0.47 (dichloromethane/EE/cyclohexane/methanol/concentrated ammonia 60/16/5/5/0.6 v/v/v/v/v)

Quellen und Nachweise

ORD-Eintrag
ord-271f97b40bfa45a6a24847cec66bb53d
Quelldatensatz
uspto-grants-2008_08
Patentnummer
US07407963B2

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