Cesium carbonate → Tert-butyl (6-chloro-5-fluoropyridin-3-yl)carbamate

HRID 60234

Reaktionsgleichung

Reaktionsgleichung von HRID 60234
Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[C:10](=[O:17])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[NH2:11].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[C:13]([O:12][C:10](=[O:17])[NH:11][C:2]1[CH:7]=[N:6][C:5]([Cl:8])=[C:4]([F:9])[CH:3]=1)([CH3:16])([CH3:15])[CH3:14]

Komponenten

7

Edukt 3

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 27632855-Bromo-2-chloro-3-fluoropyridine

Produkt 1

HCID 86656040Tert-butyl (6-chloro-5-fluoropyridin-3-yl)carbamateAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)KatalysatorHCID 9832798Tris(dibenzylideneacetone) dipalladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A degassed mixture of 5-bromo-2-chloro-3-fluoropyridine (22.5 g, 107 mmol), tert-butyl carbamate (13.8 g, 117.5 mmol), tris(dibenzylideneacetone) dipalladium(0) (2.95 g, 3.2 mmol), XantPhos (2.48 g, 4.28 mmol) and cesium carbonate (69.7 g, 214 mmol) in dioxane (340 mL) was heated at 85° C. for 24 hours. The reaction mixture was cooled to ambient temperature and the resultant solid was removed by filtration. The resultant solid was washed with ethyl acetate followed by dichloromethane and the filtrate was combined and concentrated in-vacuo to afford a residue that was purified by flash chromatography (silica: cyclohexane to 25% ethyl acetate/cyclohexane) to afford the title compound as a pale yellow solid (22.6 g, 86%). 1H NMR (300 MHz, CDCl3): 8.04 (dd, J=10.1, 2.4 Hz, 1H), 7.98 (d, J=2.4 Hz, 1H), 6.62 (s, 1H), 1.53 (s, 9H).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe resultant solid was removed by filtration
  3. washThe resultant solid was washed with ethyl acetate
  4. concentrationconcentrated in-vacuo
  5. customto afford a residue that
  6. customwas purified by flash chromatography (silica: cyclohexane to 25% ethyl acetate/cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-2aad88eff7364f1f9f9968439896e0fc
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440976B2

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