Acetonitrile → Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trimethylsilyl)phenyl)-3-methoxypicolinate

HRID 407231

Reaktionsgleichung

Reaktionsgleichung von HRID 407231
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15].[F:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:19][C:18]=1[Si:32]([CH3:35])([CH3:34])[CH3:33].[F-].[K+].CC#N>C(Cl)Cl.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:21]2[CH:20]=[CH:19][C:18]([Si:32]([CH3:34])([CH3:33])[CH3:35])=[C:17]([F:16])[CH:22]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15]

Komponenten

8

Edukt 4

HCID 6342AcetonitrileHCID 522689Potassium FluorideHCID 71150495(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilaneHCID 86675409Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate

Produkt 1

HCID 71150580Methyl 4-amino-5-fluoro-6-(3-fluoro-4-(trimethylsilyl)phenyl)-3-methoxypicolinateAusbeute 53,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a 5-mL microwave safe vial were added methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (0.400 g, 1.705 mmol), (2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)trimethylsilane (0.690 g, 2.344 mmol), KF (0.297 g, 5.11 mmol), and PdCl2(PPh3)2 (0.120 g, 0.170 mmol). A mixture of H2O (1 mL) and CH3CN (2 mL) was added, and the reaction vial was capped and placed in a Biotage Initiator microwave reactor for 20 min at 115° C. with external infrared (IR)-sensor temperature monitoring from the side of the vessel. Upon cooling to room temperature, the reaction mixture was diluted with CH2Cl2 (25 mL) and H2O (25 mL), and the organic layer was filtered through a cotton plug. An additional extraction using EtOAc (25 mL) was combined with the CH2Cl2 and dried over Na2SO4 (50 g). Following filtration of the combined organics through a cotton plug and concentration on a rotary evaporator, the residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc to yield the title compound as a light pink oil (333 mg, 53%): 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=7.6 Hz, 1H), 7.55 (d, J=9.8 Hz, 1H), 7.46 (dd, J=7.6, 5.9 Hz, 1H), 4.57 (s, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 0.33 (s, 9H); 19F NMR (376 MHz, CDCl3) δ −100.72, −140.12; ESIMS m/z 367 ([M+H]+).

Aufarbeitung

  1. additionwas added
  2. customthe reaction vial was capped
  3. filtrationthe organic layer was filtered through a cotton plug
  4. extractionAn additional extraction
  5. dry with materialdried over Na2SO4 (50 g)
  6. filtrationfiltration of the
  7. concentrationcombined organics through a cotton plug and concentration
  8. customon a rotary evaporator
  9. customthe residue was purified
  10. customa Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-dad84c795d414a6db209c8fa0f1d775d
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08754229B2

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