3,4-dihydro-2H-pyran → 2-(4-bromo-2-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyran

HRID 2284473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2284473
[Br:1][C:2]1[C:7]([CH2:8][OH:9])=[CH:6][C:5]([OH:10])=[C:4]([F:11])[CH:3]=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1>C(Cl)Cl.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>[Br:1][C:2]1[C:7]([CH2:8][O:9][CH:13]2[CH2:14][CH2:15][CH2:16][CH2:17][O:12]2)=[CH:6][C:5]([O:10][CH:17]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([F:11])[CH:3]=1

Komponenten

5

Edukt 2

HCID 80803,4-dihydro-2H-pyranHCID 667264354-Bromo-2-fluoro-5-(hydroxymethyl)phenol2×

Produkt 1

HCID 667266902-(4-bromo-2-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyranAusbeute 83 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-KatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Protection of the alcohol was carried out by making a solution of 4-bromo-2-fluoro-5-(hydroxymethyl)phenol (1.37 g, 6.19 mmol), 3,4 dihydro-2H-pyran (1.4 mL, 15 mmol) in 20 mL of CH2Cl2. The reaction mixture was then treated with camphor sulfonic acid (58 mg, 0.25 mmol) before stirring at room temperature for 21 hr. The reaction mixture was then quenched with equal volumes of 0.2 M NaOH and EtOAc (1:1, 20 mL) before the layers were separated. The water phase was further extracted with equal volume of EtOAc before the organic layers were combined and dried over anhydrous Na2SO4 and filtered. The solvent was removed under reduced pressure. The residue was purified by silica gel column using Combiflash to give 2-(4-bromo-2-fluoro-5-((tetrahydro-2H-pyran-2-yloxy)methyl)phenoxy)tetrahydro-2H-pyran (2.0 g, 83%).

Aufarbeitung

  1. customThe reaction mixture was then quenched with equal volumes of 0.2 M NaOH and EtOAc (1:1, 20 mL) before the layers
  2. customwere separated
  3. extractionThe water phase was further extracted with equal volume of EtOAc before the organic layers
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customThe solvent was removed under reduced pressure
  7. customThe residue was purified by silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-3016616cd68c4ee29ccd2a8ad7dd5112
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145429B2

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