Cesium fluoride → Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate

HRID 2410719Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2410719
[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].[CH2:14]([O:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[F-].[Cs+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[C:11]([C:25]2[CH:26]=[CH:27][C:22]([O:21][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:23][CH:24]=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 27343144-Benzyloxy-phenylboronic acidHCID 53419616Methyl 3-amino-2,6-dibromoisonicotinate

Produkt 1

HCID 86663009Methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinateAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A flask containing a mixture of methyl 3-amino-2,6-dibromoisonicotinate (1000 mg, 3.23 mmol), 4-(benzyloxy)phenylboronic acid (883 mg, 3.87 mmol), cesium fluoride (1176 mg, 7.74 mmol) and tetrakis(triphenylphosphine)-palladium(0) (224 mg, 0.194 mmol) was flushed with nitrogen. Dimethoxyethane (16 mL) was added and the reaction was heated at 80° C. for 18 hr. The reaction was then partitioned between EtOAc and water. 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 30 to 20% methylene chloride) afforded 1055 mg of methyl 3-amino-2-(4-(benzyloxy)-phenyl)-6-bromoisonicotinate as a yellow solid. MS (ESI) m/z 415.1 (M+H). 1H NMR (CDCl3) δ ppm 7.77 (1H, s), 7.55 (2H, d, J=8.55 Hz), 7.31-7.46 (5H, m), 7.06 (2H, d, J=8.55 Hz), 5.95 (2H, br. s.), 5.12 (2H, s), 3.92 (3H, s).

Aufarbeitung

  1. additionA flask containing
  2. customwas flushed with nitrogen
  3. additionDimethoxyethane (16 mL) was added
  4. customThe reaction 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 30 to 20% methylene chloride)

Quellen und Nachweise

ORD-Eintrag
ord-ce8594f8cf0d4ab0a4d0babfc6a846ce
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08815840B2

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