Cesium fluoride → Methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate

HRID 2410728Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2410728
[NH2:1][C:2]1[C:11](Br)=[N:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Cl:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][C:20]=1[O:21][CH3:22].[F-].[Cs+]>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>[NH2:1][C:2]1[C:11]([C:17]2[CH:18]=[CH:19][C:20]([O:21][CH3:22])=[C:15]([Cl:14])[CH:16]=2)=[N:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Komponenten

5

Edukt 3

HCID 25953Cesium fluorideHCID 32475223-Chloro-4-methoxybenzeneboronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Produkt 1

HCID 86663013Methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinateAusbeute 30,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A vial containing a mixture of methyl 3-amino-2,6-dibromoisonicotinate (500 mg, 1.613 mmol), 3-chloro-4-methoxyphenylboronic acid (301 mg, 1.613 mmol), cesium fluoride (588 mg, 3.87 mmol), and tetrakis(triphenylphosphine)palladium(0) (112 mg, 0.097 mmol) was flushed with nitrogen. Dimethoxyethane (8 mL) was added and the reaction was heated at 80° C. for 18 hr. It was then partitioned between EtOAc and water and the organic phase was separated, washed with brine, dried with sodium sulfate, and the solvent removed. Radial silica gel chromatography (step gradient elution with hexane containing 25 to 40% methylene chloride) afforded methyl 3-amino-6-bromo-2-(3-chloro-4-methoxyphenyl)isonicotinate (181 mg) as a yellow solid. MS (ESI) m/z 373.0 (M+H). 1H NMR (CDCl3) δ ppm 7.79 (1H, s), 7.66 (1H, d, J=2.14 Hz), 7.52 (1H, dd, J=8.55, 2.14 Hz), 7.02 (1H, d, J=8.55 Hz), 5.94 (2H, br. s.), 3.95 (3H, s), 3.92 (3H, s).

Aufarbeitung

  1. additionA vial containing
  2. customwas flushed with nitrogen
  3. additionDimethoxyethane (8 mL) was added
  4. customIt was then partitioned between EtOAc and water
  5. customthe organic phase was separated
  6. washwashed with brine
  7. dry with materialdried with sodium sulfate
  8. customthe solvent removed
  9. washRadial silica gel chromatography (step gradient elution with hexane containing 25 to 40% methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-4d1ceace956b438da66894e3e8e1b0e9
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08815840B2

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