Potassium Phosphate, Tribasic → Methyl 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetate

HRID 2176649

Reaktionsgleichung

Reaktionsgleichung von HRID 2176649
Cl[C:2]1[N:7]=[C:6]2[C:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:9][O:10][C:5]2=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[C:29]([F:31])[CH:30]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[F:24][C:25]1[CH:26]=[C:27]([C:2]2[N:7]=[C:6]3[C:8]([CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:9][O:10][C:5]3=[CH:4][CH:3]=2)[CH:28]=[C:29]([F:31])[CH:30]=1

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 10198435Methyl 2-(5-chlorofuro[3,2-b]pyridin-3-yl)acetateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

Produkt 1

HCID 57691370Methyl 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetateAusbeute 83,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 8857Ethyl AcetateLösungsmittel2×

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A sealable microwave vial was charged with methyl 2-(5-chlorofuro[3,2-b]pyridin-3-yl)acetate (1.30 g, 5.74 mmol), palladium(II) acetate (0.129 g, 0.574 mmol), potassium phosphate (3.66 g, 17.2 mmol), 3,5-difluorophenylboronic acid (1.81 g, 11.5 mmol), and X-Phos (0.548 g, 1.15 mmol). The vial was sealed, flushed with N2, then dioxane (20 mL) and H2O (2 mL) were added. The solution was sparged with N2 for 10 min, then heated at 100° C. for 24 h. The mixture was then cooled to rt and concentrated for purification by MPLC (Teledine Isco combiFlash Companion). The crude residue was taken up in minimal CH2Cl2 and absorbed onto a 25 g loading cartridge and passed through a Redi-Sep® pre-packed silica gel column (120 g) using 98:2 Hexanes:EtOAc to 70:30 Hexanes:EtOAc gradient to afford methyl 2-(5-(3,5-difluorophenyl)furo[3,2-b]pyridin-3-yl)acetate (1.46 g, 83.8% yield) as a colorless amorphous solid. LRMS (ESI) m/z calcd for C16H12F2NO3 (M+H) 304.1. found 304.2.

Aufarbeitung

  1. customThe vial was sealed
  2. customflushed with N2
  3. additiondioxane (20 mL) and H2O (2 mL) were added
  4. customThe solution was sparged with N2 for 10 min
  5. temperatureThe mixture was then cooled to rt
  6. concentrationconcentrated for purification by MPLC (Teledine Isco combiFlash Companion)
  7. customabsorbed onto a 25 g loading cartridge

Quellen und Nachweise

ORD-Eintrag
ord-11473237ada445948a639b6a0880b065
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09066954B2

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