1,2-Dimethoxyethane → 4-(5-Chloro-2-fluoropyridin-4-yl)-benzoic acid methyl ester

HRID 968692Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 968692
[Cl:1][C:2]1[C:3](I)=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.C([CH2:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1)(O)=O.[C:23]([O-])([O-])=[O:24].[Na+].[Na+].C(COC)[O:30]C>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>[CH3:23][O:24][C:13](=[O:30])[C:14]1[CH:15]=[CH:16][C:17]([C:3]2[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([F:8])[CH:4]=2)=[CH:18][CH:19]=1

Komponenten

6

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 218653365-Chloro-2-fluoro-4-iodopyridineHCID 218789612-(4-Boronophenyl)acetic acid

Produkt 1

HCID 694221754-(5-Chloro-2-fluoropyridin-4-yl)-benzoic acid methyl esterAusbeute 34 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

5-Chloro-2-fluoro-4-iodopyridine, (257 mg, 1 mmol), 4-carboxymethylphenyl boronic acid (0.2 g, 1.1 mmol) were dissolved in dimethoxyethane in a screw cap test tube and 1.5 mL 2M Na2CO3 was added followed by tetrakis(triphenylphosphine)palladium (50 mg, 0.044 mmol). Argon was bubbled through the reaction mixture for 5 min, the tube was sealed, and then the reaction mixture was heated to 85° C. overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated to an oil, which was purified by chromatography on silica (EtOAc 0 to 15% in hexanes) to give 90 mg (0.34 mmol, 34% yield) of 4-(5-chloro-2-fluoropyridin-4-yl)-benzoic acid methyl ester. 1H NMR 500 MHz (CDCl3): 8.24 (s, 1H), 8.10 (d, 2H), 7.48 (d, 2H), 6.89 (d, 1H), 3.91 (s, 3H). LCMS: ES+=257.9.

Aufarbeitung

  1. customcap test tube
  2. customArgon was bubbled through the reaction mixture for 5 min
  3. customthe tube was sealed
  4. additionThe reaction mixture was poured into water
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to an oil, which
  9. customwas purified by chromatography on silica (EtOAc 0 to 15% in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-4cc935bb706e4b1d931851e202b45175
Quelldatensatz
uspto-grants-2007_12
Patentnummer
US07304071B2

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