Tetrahydrofuran → 6-Benzyloxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl 3-methoxy-4-(1-pyrrolidinylmethyl)phenyl ketone

HRID 1387094Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1387094
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:25][C:19]=3[S:20][C:21]=2N(C)C)=[O:16])[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1.[F-].[CH2:38]([N+](CCCC)(CCCC)CCCC)[CH2:39]CC.[CH2:55]1[CH2:59][O:58][CH2:57][CH2:56]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]([C:17]2[C:18]3[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)=[CH:25][C:19]=3[S:20][C:21]=2[C:59]2[CH:55]=[CH:56][C:57]([OH:58])=[CH:39][CH:38]=2)=[O:16])[CH:6]=[CH:7][C:8]=1[CH2:9][N:10]1[CH2:11][CH2:12][CH2:13][CH2:14]1

Komponenten

4

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 2724141Tetrabutylammonium FluorideHCID 106730126-Benzyloxy-2-dimethylaminobenzo[b]thiophen-3-yl 3-Methoxy-4-[(1-pyrrolidinyl)methyl]phenyl Ketone

Produkt 1

HCID 224627986-Benzyloxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl 3-methoxy-4-(1-pyrrolidinylmethyl)phenyl ketoneAusbeute 100 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Magnesium turnings (0.24 g) were placed in a two-neck 100 mL round-bottom flask fitted with a reflux condenser and a magnetic stir bar. The whole apparatus was flame-dried and allowed to cool to ambient temperature. Dry THF (17 mL) and a small crystal of iodine were then introduced followed by slow addition of 4-bromophenyl triisopropylsilyl ether (3.5 g) while stirring at ambient temperature. The reaction mixture was warmed to a gentle reflux for 1 h or until the magnesium turnings were completely consumed to give a 0.5 M solution of the Grignard reagent. This freshly prepared Grignard solution (15 mL) was added slowly to a stirring solution of 6-benzyloxy-2-(dimethylamino)benzo[b]thiophen-3-yl 3-methoxy-4-[(1-pyrrolidinyl)methyl]phenyl ketone (2.5 g, 5.0 mmol) in THF (15.0 mL) at 0° C. under argon. The mixture was stirred at 0° C. for 2 h before quenching with saturated aqueous NH4Cl solution (50 mL) and extraction with CH2Cl2 (50 mL×3). The combined organic layers were dried with sodium sulfate and concentrated under reduced pressure. Chromatography with EtOAc afforded a oily brown material as the major fraction. This material was dissolved in THF (25 mL), treated with a solution of tetrabutylammonium fluoride (1.0 M in THF, 6 mL) at ambient temperature for 1 h, and then concentrated under reduced pressure. Chromatography with Et3N:MeOH:EtOAc (5:10:85) afforded the title compound as a yellow foam (2.75 g, 100%).

Aufarbeitung

  1. custombefore quenching with saturated aqueous NH4Cl solution (50 mL) and extraction with CH2Cl2 (50 mL×3)
  2. dry with materialThe combined organic layers were dried with sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customChromatography with EtOAc afforded a oily brown material as the major fraction
  5. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-abe5ea81e24d48529a83d2df86a2aefc
Quelldatensatz
uspto-grants-2001_07
Patentnummer
US06265575B1

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