Trimethylsilyl isocyanate → 1-(4-Methoxyphenyl)-4-[2-(5-aminocarbonylisochroman-1-yl)ethyl]piperazine

HRID 368854

Reaktionsgleichung

Reaktionsgleichung von HRID 368854
C([Li])(C)(C)C.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH:22]3[C:31]4[C:26](=[C:27](Br)[CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24][O:23]3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.C[Si]([N:37]=[C:38]=[O:39])(C)C>C1COCC1.O1CCOCC1>[CH3:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][CH:22]3[C:31]4[C:26](=[C:27]([C:38]([NH2:37])=[O:39])[CH:28]=[CH:29][CH:30]=4)[CH2:25][CH2:24][O:23]3)[CH2:16][CH2:15]2)=[CH:10][CH:9]=1

Komponenten

6

Edukt 3

HCID 70696Trimethylsilyl isocyanateHCID 232887441-(4-Methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)ethyl]piperazineHCID 178418306HCID 178418306, Verbindung

Produkt 1

HCID 232888291-(4-Methoxyphenyl)-4-[2-(5-aminocarbonylisochroman-1-yl)ethyl]piperazine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of t-butyl lithium (2 eqs, 1.7 M in hexane) in THF (2 ml/mmol bromide) is cooled to -78° for 10 minutes before adding the 1-(4-methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)ethyl]piperazine (LXXIV, EXAMPLE 100) in THF (4 ml/mmol) dropwise over 10 minutes. A freshly distilled solution of trimethylsilylisocyanate (1.5 eqs) is added via syringe as a solution in dioxane (4 volume equivalents) at once. After 15 minutes, the cooling bath is removed and the mixture allowed to warm to 20-25°. The reaction mixture is quenched with ammonium chloride, the organics are removed under reduced pressure, and the aqueous residue is extracted two times with methylene chloride, dried over sodium sulfate, filtered and concentrated. The crude material is purified by flash chromatography on silica gel. In this manner, 1-(4-methoxyphenyl)-4-[2-(5-bromoisochroman-1-yl)ethyl]piperazine (LXXIV, EXAMPLE 100, 345 mg) is converted to the corresponding amide, the title compound, mp 185-186°.

Aufarbeitung

  1. temperatureis cooled to -78° for 10 minutes
  2. customthe cooling bath is removed
  3. temperatureto warm to 20-25°
  4. customThe reaction mixture is quenched with ammonium chloride
  5. customthe organics are removed under reduced pressure
  6. extractionthe aqueous residue is extracted two times with methylene chloride
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material is purified by flash chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-c323b231d7ec4362b0bb1c6e435381a2
Quelldatensatz
uspto-grants-2000_10
Patentnummer
US06133446

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