3-(Bromomethyl)-5-methylisoxazole → Ammonium Hydroxide

HRID 1661543Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1661543
Cl.[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:29][C:30]1[CH:34]=[C:33]([CH3:35])[O:32][N:31]=1>C1COCC1>[NH4+:5].[OH-:32].[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:29][C:30]2[CH:34]=[C:33]([CH3:35])[O:32][N:31]=2)[C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1

Komponenten

6

Edukt 3

HCID 27763043-(Bromomethyl)-5-methylisoxazoleHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539613-Methyl-2-(3-pyridyl)indole hydrochloride

Produkt 2

HCID 14923Ammonium HydroxideAusbeute 0,1 %HCID 445541373-methyl-1-(5-methyl-isoxazol-3-ylmethyl)-2-pyridin-3-yl-1H-indole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.100 g, 0.408 mmol) in THF (2.5 mL) and cooled to 0° C. KHMDS (0.5 M in toluene, 1.8 mL, 0.898 mmol) is added and the mixture is stirred at room temperature for 30 min, followed by addition of 3-bromomethyl-5-methyl-isoxazole (0.144 g, 0.817 mmol). The reaction mixture is stirred for 0.5 h, then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 3-methyl-1-(5-methyl-isoxazol-3-ylmethyl)-2-pyridin-3-yl-1H-indole product as a colorless oil. The oil is dissolved in diethyl ether and few drops of concentrated HCl are added. The volatiles are removed in vacuo and the reside is lyophilized to afford the product as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm (HCl salt) 2.30 (s, 3H), 2.31 (s, 3H), 5.30 (s, 2H), 5.67 (s, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.27 (ddd, J=7.6, 1.1 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.56-7.69 (m, 2H), 7.99 (dt, J=8.0, 1.9, 1.8 Hz, 1H), 8.56-8.68 (m, 2H). HRMS (ESI) m/z 304.1440 [(M+H)+ Calcd for C19H18N3O, 304.1450].

Aufarbeitung

  1. stirringThe reaction mixture is stirred for 0.5 h
  2. customquenched with saturated ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by reverse phase HPLC with Xbridge Shield RP18 column

Quellen und Nachweise

ORD-Eintrag
ord-4d3039a3b951439ba4938b735e66d6bf
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08030334B2

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