Cesium carbonate → 1-{5-Fluoro-8-[(3R)-3-hydroxypyrrolidin-1-yl]quinolin-7-yl}ethanone

HRID 1192578Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1192578
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([F:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[NH:23]1[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:23]2[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2759337(R)-3-PyrrolidinolHCID 583685787-Acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonate

Produkt 1

HCID 583684551-{5-Fluoro-8-[(3R)-3-hydroxypyrrolidin-1-yl]quinolin-7-yl}ethanoneAusbeute 12,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A stirred mixture of 7-acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonate (0.101 g, 0.301 mmol), (3R)-pyrrolidin-3-ol (0.0315 g, 0.362 mmol), palladium acetate (1 mg, 0.006 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6 mg, 0.009 mmol), and cesium carbonate (0.147 g, 0.451 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over sodium sulfate and evaporated to dryness. The resulting residue was purified on silica gel, eluting with 0 to 10% MeOH in dichloromethane, to give the desired product (10 mg, 10%). LCMS calculated for C15H16FN2O2 (M+H)±: m/z=275.1; Found: 275.1.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe resulting residue was purified on silica gel
  7. washeluting with 0 to 10% MeOH in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-0d09e80ce5db4c01a2ecd2b73beff894
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08680108B2

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