Sodium hydride → 5-Bromo-4-(cyclopropylmethoxy)-2-methoxypyridine

HRID 518540Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 518540
[CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].[Br:8][C:9]1[C:10](Cl)=[CH:11][C:12]([O:15][CH3:16])=[N:13][CH:14]=1>C1COCC1.[NH4+]>[Br:8][C:9]1[C:10]([O:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)=[CH:11][C:12]([O:15][CH3:16])=[N:13][CH:14]=1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 75644CyclopropanemethanolHCID 231336495-Bromo-4-chloro-2-methoxypyridine

Produkt 1

HCID 1180238475-Bromo-4-(cyclopropylmethoxy)-2-methoxypyridineAusbeute 70,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 223AmmoniumLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

To a solution of cyclopropylmethanol (446 mg, 6.18 mmol) in THF (10 mL) was added NaH (247 mg, 6.18 mmol, 60% in mineral oil) in one portion at 0° C. The reaction mixture was warmed up to 20° C. over a period of 30 mins and stirred at 20° C. for 10 mins. Then 5-bromo-4-chloro-2-methoxypyridine (550 mg, 2.47 mmol) was added in one portion and the mixture was stirred at 70° C. for 4 hours. The mixture was diluted with saturated ammonium aqueous solution (50 mL) and extracted by EtOAc (2×30 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated to give the crude product which was purified by silica gel column chromatography (PE: EA=20:1 to 10:1) to afford the title compound (450 mg, 70.6%) as colorless oil. 1H NMR: (CDCl3, 400 MHz) δ: 8.11 (s, 1H), 6.18 (s, 1H), 3.90 (s, 3H), 3.89-3.88 (m, 2H), 1.39-1.27 (m, 1H), 0.70-0.67 (m, 2H), 0.46-0.43 (m, 2H). LCMS (M+H)+=258.0 (M+1)+; 260.0

Aufarbeitung

  1. stirringthe mixture was stirred at 70° C. for 4 hours
  2. extractionextracted by EtOAc (2×30 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product which
  7. customwas purified by silica gel column chromatography (PE: EA=20:1 to 10:1)

Quellen und Nachweise

ORD-Eintrag
ord-5019fcb1fbd544ac9844fae679ec992e
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115114B2

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