Sodium Carbonate → 5-(Bromomethyl)-2-(difluoromethoxy)-3-(3-(oxetan-3-yloxy)phenyl)pyridine

HRID 2271466Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2271466
[F:1][CH:2]([F:18])[O:3][C:4]1[C:9]([C:10]2[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=2)=[CH:8][C:7]([CH3:17])=[CH:6][N:5]=1.[Br:19]C1C(OC(F)F)=NC=C(CBr)C=1.[OH:32][C:33]1C=C(B(O)O)C=[CH:37][CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(#N)C.O>[Br:19][CH2:17][C:7]1[CH:8]=[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH:38]3[CH2:33][O:32][CH2:37]3)[CH:11]=2)[C:4]([O:3][CH:2]([F:1])[F:18])=[N:5][CH:6]=1

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 904147933-Bromo-5-(bromomethyl)-2-(difluoromethoxy)pyridine2×HCID 904152023-(2-(Difluoromethoxy)-5-methylpyridin-3-yl)phenol

Produkt 1

HCID 904149725-(Bromomethyl)-2-(difluoromethoxy)-3-(3-(oxetan-3-yloxy)phenyl)pyridineAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

3-(2-(Difluoromethoxy)-5-methylpyridin-3-yl)phenol. A 20 mL microwave vial was charged with 3-bromo-2-(difluoromethoxy)-5-methylpyridine (intermediate 4, 1.90 g, 7.98 mmol), 3-hydroxyphenylboronic acid (1.32 g, 9.58 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (330 mg, 0.40 mmol), sodium carbonate (2.12 g, 19.96 mmol), water (4.0 mL), and ACN (12 mL). The vial was sealed, purged with nitrogen, and heated under microwave irradiation at 100° C. for 15 min. The reaction mixture was diluted with water and extracted with DCM (3×). The combined organic phase was dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification (FCC, SiO2, 0-40% EtOAc/hexanes) afforded the title compound (1.81 g, 91%) as a colorless waxy solid. [M+H]=252.12.

Aufarbeitung

  1. customThe vial was sealed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted with DCM (3×)
  5. dry with materialThe combined organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification (FCC, SiO2, 0-40% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-4f6d6a53547945ea9d3b8760c860e17d
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09120770B2

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