Phosphate → 5-(2,2-Difluorovinyl)-N-methyl-N-propyl-isophthalamic acid ethyl ester

HRID 732498

Reaktionsgleichung

Reaktionsgleichung von HRID 732498
[CH2:1]([Li])CCC.[F:6][C:7]([F:20])=[CH:8]OS(C1C=CC(C)=CC=1)(=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:40][O:41][C:42](=[O:57])[C:43]1[CH:55]=[C:54](I)[CH:53]=[C:45]([C:46]([N:48]([CH3:52])[CH2:49][CH2:50][CH3:51])=[O:47])[CH:44]=1.P([O-])([O-])([O-])=O>C1COCC1.[Cl-].[Cl-].[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Zr+2].[I-].[Zn+2].[I-].C(OCC)(=O)C>[CH2:40]([O:41][C:42](=[O:57])[C:43]1[CH:55]=[C:54]([CH:8]=[C:7]([F:20])[F:6])[CH:53]=[C:45]([C:46]([N:48]([CH3:52])[CH2:49][CH2:50][CH3:51])=[O:47])[CH:44]=1)[CH3:1]

Komponenten

10

Edukt 5

HCID 1061PhosphateHCID 11776TriphenylphosphineHCID 109773662,2-Difluoroethenyl 4-methylbenzene-1-sulfonateHCID 21086185Methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoateHCID 178418339Butyllithium

Produkt 1

HCID 688145195-(2,2-Difluorovinyl)-N-methyl-N-propyl-isophthalamic acid ethyl esterAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9883512zinc(II)iodideKatalysatorHCID 131716798Zirconocene dichiorideKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Add n-butyllithium (1.6 M in hexanes, 4.5 mL, 7.4 mmol) dropwise to a mixture of zirconocene dichloride (1.05 g, 3.6 mmol) in dry THF (15 mL) at −78° C. and stir for 1 h. Add a solution of toluene-4-sulfonic acid 2,2-difluorovinyl ester (420 mg, 1.8 mmol) in THF (3.6 mL) dropwise. Stir at −78° C. for 5 min and at room temperature for 3 h. Add triphenyl phosphine (79 mg, 0.3 mmol) and tris(dibenzylidineacetone)dipalladium(0) (34 mg, 0.036 mmol), stir for 10 min, add 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (722 mg, 2.0 mmol) and zinc iodide (1.35 g, 4.3 mmol). Reflux the reaction for 1 h and stir at room temperature overnight. Add pH=7 phosphate buffer (400 mL) and ethyl acetate (250 mL). Separate the layers and wash with saturated aqueous ammonium chloride (2×100 mL), saturated aqueous sodium bicarbonate (2×100 mL), dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 25:75 ethyl acetate:hexanes) to give the title compound (187 mg, 35%).

Aufarbeitung

  1. stirringStir at −78° C. for 5 min and at room temperature for 3 h
  2. temperatureReflux
  3. customthe reaction for 1 h
  4. stirringstir at room temperature overnight
  5. customSeparate the layers
  6. washwash with saturated aqueous ammonium chloride (2×100 mL), saturated aqueous sodium bicarbonate (2×100 mL)
  7. dry with materialdry (magnesium sulfate)
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography, eluting with 25:75 ethyl acetate:hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-ad014bfc7c9546a49786bf888db614b1
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07585885B2

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