Sodium Carbonate → 2-Chloro-3-(4-fluorophenyl)pyridine

HRID 2284560

Reaktionsgleichung

Reaktionsgleichung von HRID 2284560
[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)NN=C3)=[CH:6][CH:5]=[CH:4][N:3]=1.[F:17]C1C=CC(B(O)O)=CC=1.BrC1C(Cl)=NC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([C:8]2[CH:9]=[CH:10][C:14]([F:17])=[CH:15][CH:16]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 6933243-Bromo-2-chloropyridineHCID 867154695-(2-chloropyridin-3-yl)-1H-indazole2×

Produkt 1

HCID 463120422-Chloro-3-(4-fluorophenyl)pyridine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

2-Chloro-3-(4-fluorophenyl)pyridine was synthesized analogous to the reaction conditions used in the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole by heating the mixture of 4-fluorophenyl boronic acid (3.0 g, 21.4 mmol), 3-bromo-2-chloropyridine (4.9 g, 25.7 mmol), Pd(PPh3)4 (1.6 g, 1.3 mmol) and 2M aq. Na2CO3 (25 mL, 50 mmol) in 1,4-dioxane (125 mL) under argon atmosphere for 12 h. LC/MS indicated three products with MH+ 208, 254 and 268. Upon work-up of the reaction mixture, as discussed in the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole, the crude concentrated was purified by flash silica gel column chromatography [Combiflash® companion System® with RediSep® silica gel column 120 g, 10-50% EtOAC/hexanes eluting solvent gradient upon liquid loading on to column]. Two fractions containing the desired product were identified and concentrated. 2-Chloro-3-(4-fluorophenyl)pyridine was isolated as a crystalline solid (888 mg, 16%) from the fraction containing 2,3-bis(4-fluorophenyl)pyridine by suspending the semi solid fraction mixture in 10% EtOAc/hexanes and filtered. 1H NMR (DMSO-d6): δ 8.41 (dd, 1H, J=1.8 and 4.7 Hz), 7.86 (dd, 1H, J=2.0 and 7.6 Hz), 7.54-7.48 (m, 3H), 7.34-7.31 (m, 2H). 19F NMR (DMSO-d6): δ −114.06 (s). LCMS: rt 7.50 min (A), purity 99%, MS (m/e) 208 (MH+).

Aufarbeitung

  1. custom2-Chloro-3-(4-fluorophenyl)pyridine was synthesized analogous to the reaction conditions
  2. temperatureby heating
  3. concentrationthe crude concentrated
  4. customwas purified by flash silica gel column chromatography [Combiflash® companion System® with RediSep® silica gel column 120 g, 10-50% EtOAC/hexanes eluting solvent gradient upon liquid loading on to column]
  5. additionTwo fractions containing the desired product
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-bcec5fcddc1545dfa5e93334509af437
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145433B2

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