Cesium carbonate → Methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate

HRID 1894956Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1894956
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.Br[C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][C:48]([C:54]([O:56][CH3:57])=[O:55])=[CH:47]2.[C:58](=[O:65])([O:60][C:61]([CH3:64])([CH3:63])[CH3:62])[NH2:59].C(=O)([O-])[O-].[Cs+].[Cs+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:61]([O:60][C:58]([NH:59][C:44]1[CH:45]=[C:46]2[C:51](=[CH:52][CH:53]=1)[N:50]=[CH:49][C:48]([C:54]([O:56][CH3:57])=[O:55])=[CH:47]2)=[O:65])([CH3:64])([CH3:63])[CH3:62]

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 53465709Methyl 6-bromoquinoline-3-carboxylate

Produkt 1

HCID 67002181Methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylateAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a round bottom flask under dry nitrogen were added palladium(II) acetate (100 mg, 0.6 mmol), Xantphos (600 mg, 1 mmol), methyl 6-bromoquinoline-3-carboxylate (1.5 g, 5.64 mmol), t-butyl carbamate (0.99 g, 8.4 mmol) and cesium carbonate (3.67 g, 11.3 mmol). Dry 1,4-dioxane (30 mL) was added by syringe and the mixture was stirred at 100° C. under dry nitrogen for 4 h. The reaction mixture was cooled to room temperature, diluted with water and extracted three times with ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude mixture was purified by silica gel chromatography (hexanes to 1:1 hexanes/ethyl acetate gradient) to afford methyl 6-(tert-butoxycarbonylamino)quinoline-3-carboxylate (Int-2, 1.29 g, 76%). LC-MS: (FA) ES+ 303; 1H NMR (400 MHz, d6-DMSO) δ ppm 9.86 (s, 1H), 9.14 (d, J=2.1 Hz, 1H), 8.82 (d, J=1.9 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.00 (d, J=9.1 Hz, 1H), 7.87 (dd, J=9.1, 2.4 Hz, 1H), 3.93 (s, 3H), 1.51 (s, 9H).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted three times with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude mixture was purified by silica gel chromatography (hexanes to 1:1 hexanes/ethyl acetate gradient)

Quellen und Nachweise

ORD-Eintrag
ord-9ef9a5547faf4556b681255236d59fbd
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08513421B2

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