Ammonium Chloride → (5-Bromo-2-methoxyphenyl)(2,6-difluoropyridin-3-yl)methanol

HRID 335901Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 335901
C([Li])CCC.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[N:8]=1.[Br:14][C:15]1[CH:16]=[CH:17][C:18]([O:23][CH3:24])=[C:19]([CH:22]=1)[CH:20]=[O:21].[Cl-].[NH4+]>C1COCC1>[Br:14][C:15]1[CH:16]=[CH:17][C:18]([O:23][CH3:24])=[C:19]([CH:20]([C:12]2[C:7]([F:6])=[N:8][C:9]([F:13])=[CH:10][CH:11]=2)[OH:21])[CH:22]=1

Komponenten

6

Edukt 4

HCID 25517Ammonium ChlorideHCID 739342,6-DifluoropyridineHCID 906845-Bromo-2-methoxybenzaldehydeHCID 178418339Butyllithium

Produkt 1

HCID 67383458(5-Bromo-2-methoxyphenyl)(2,6-difluoropyridin-3-yl)methanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel4×

Versuchsvorschrift

DIPA (8.0 mL, 56.6 mmol) was dissolved in dry THF (40 mL) under nitrogen and cooled in a dry ice bath to −78°. n-Butyllithium solution, 2.5 m in hexanes (23.0 mL, 57.5 mmol) was added and the solution stirred for a few minutes prior to dropwise addition of 2,6-difluoropyridine (5.0 mL, 55.1 mmol) in dry THF (10 mL) via an addition funnel over 10 minutes. The pale yellow solution was stirred for 30 minutes then additional dry THF (70 mL) was added dropwise via an addition funnel. Solid 5-bromo-2-methoxybenzaldehyde (11.85 g, 55.1 mmol) was added in one portion and the reaction stirred for 5 minutes. Additional dry THF (100 mL) was added dropwise to keep the mixture stirring freely. After 15 minutes saturated ammonium chloride (20 mL) was added to quench followed by ethyl acetate (200 mL) and water (200 mL). The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. Purification using silica chromatography (hexane to DCM gradient) gave (5-bromo-2-methoxyphenyl)(2,6-difluoropyridin-3-yl)methanol.

Aufarbeitung

  1. temperaturecooled in a dry ice bath to −78°
  2. stirringThe pale yellow solution was stirred for 30 minutes
  3. stirringthe reaction stirred for 5 minutes
  4. stirringstirring freely
  5. customto quench
  6. additionThe phases were mixed
  7. customseparated
  8. dry with materialthe organic dried with magnesium sulfate
  9. custombefore evaporating to dryness under reduced pressure
  10. customPurification

Quellen und Nachweise

ORD-Eintrag
ord-6537e90b9b464f1a9c809b20ade76884
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883782B2

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