Tetrahydrofuran → N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide

HRID 1502231Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1502231
[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH2:8])[CH:5]=[N:6][CH:7]=1.O1CCCC1.C[Mg]Br.[O:18]1[CH2:23][CH2:22][CH:21]([C:24](OC)=[O:25])[CH2:20][CH2:19]1>C1(C)C=CC=CC=1.ClCCl>[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH:8][C:24]([CH:21]2[CH2:22][CH2:23][O:18][CH2:19][CH2:20]2)=[O:25])[CH:5]=[N:6][CH:7]=1

Komponenten

7

Edukt 4

HCID 8028TetrahydrofuranHCID 27735202H-Pyran-4-carboxylic acid, tetrahydro-, methyl esterHCID 70606795-Bromo-4-methylpyridin-3-amineHCID 178418573HCID 178418573, Verbindung

Produkt 1

HCID 67974771N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamideAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 5-bromo-4-methylpyridin-3-amine (128.9 mg, 0.6892 mmol) in tetrahydrofuran (4.0 mL, 49 mmol) at 0° C. was added 1.4 M of methylmagnesium bromide in toluene (0.55 mL). After stirring at 0° C. for 10 minutes, methyl tetrahydro-2H-pyran-4-carboxylate (92.00 g, 638.1 mmol) was added. The reaction mixture was stirred overnight while warming to room temperature. The reaction mixture was poured into dichloromethane, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 53.5 mg (26%) of N-(5-bromo-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide. LCMS (ESI): M+H=299.2.

Aufarbeitung

  1. stirringThe reaction mixture was stirred overnight
  2. temperaturewhile warming to room temperature
  3. washwashed with saturated aqueous NaHCO3
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-10% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-c97aaf10e02d47caa1b0f5605f16cdd0
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

Notizen zur Reaktion

Wird geladen…