Water → Ethyl (2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 1475878Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1475878
C(=O)([O-])[O-].[K+].[K+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[F:16][C:17]1[C:18](=[O:37])[N:19]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:34])=[O:33])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=[CH:21][C:22]=1I.O>O1CCOCC1.[Pd]>[F:16][C:17]1[C:18](=[O:37])[N:19]([CH2:24][CH2:25][C@@:26]([CH3:36])([S:32]([CH3:35])(=[O:33])=[O:34])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:20]=[CH:21][C:22]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 67249327Ethyl (2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

Produkt 1

HCID 67248709Ethyl (2R)-4-(3-fluoro-2-oxo-4-phenylpyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateAusbeute 51,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Pd EnCat™ (172 mg, 0.067 mmol) was added to a mixture of potassium carbonate (298 mg, 2.16 mmol), phenylboronic acid (132 mg, 1.08 mmol), and ethyl (2R)-4-(3-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (288 mg, 0.647 mmol) in 1,4-dioxane:water (10 ml, 4:1) in a 20 ml vial. The vial was sealed and the reaction was heated to 80° C. and allowed to stir overnight at that temperature. The reaction was allowed to cool to RT, filtered and the catalyst was washed with methanol (20 mL) and dichloromethane (20 mL). The combined filtrates were concentrated and the crude product was purified via flash chromatography using an Analogix SF15-12g column and an eluant of ethyl acetate in heptane (60-100%) to afford the title compound as a white solid (131 mg, 51.2%). LC-MS m/z 396.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (t, J=7.12 Hz, 3H) 1.79 (s, 3H) 2.46-2.67 (m, 2H) 3.14 (s, 3H) 3.99-4.16 (m, 1H) 4.22-4.44 (m, 3H) 6.24-6.39 (m, 1H) 7.10-7.22 (m, 1H) 7.38-7.55 (m, 3H) 7.54-7.63 (m, 2H).

Aufarbeitung

  1. customThe vial was sealed
  2. temperatureto cool to RT
  3. filtrationfiltered
  4. washthe catalyst was washed with methanol (20 mL) and dichloromethane (20 mL)
  5. concentrationThe combined filtrates were concentrated
  6. customthe crude product was purified via flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-975d36417d8f4bf082e7411da9cf2123
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018384B2

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