Cesium carbonate → Ethyl (2R)-4-(3,5-difluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

HRID 468650

Reaktionsgleichung

Reaktionsgleichung von HRID 468650
C(=O)([O-])[O-].[Cs+].[Cs+].[F:7][C:8]1[C:9](=[O:16])[NH:10][CH:11]=[C:12]([F:15])[C:13]=1[I:14].Br[CH2:18][CH2:19][C@@:20]([CH3:30])([S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([O:23][CH2:24][CH3:25])=[O:22]>O1CCCC1.C(O)(C)(C)C>[F:7][C:8]1[C:9](=[O:16])[N:10]([CH2:18][CH2:19][C@@:20]([CH3:30])([S:26]([CH3:29])(=[O:28])=[O:27])[C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:11]=[C:12]([F:15])[C:13]=1[I:14]

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 706651963,5-difluoro-4-iodopyridin-2(1H)-oneHCID 86670635(R)-ethyl 4-bromo-2-methyl-2-(methylsulfonyl)butanoate

Produkt 1

HCID 86670654Ethyl (2R)-4-(3,5-difluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateAusbeute 32 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 66775918Tert-butanol tetrahydrofuranLösungsmittel

Versuchsvorschrift

Cesium carbonate (1.90 g, 5.84 mmol) was added to a solution of the 3,5-difluoro-4-iodopyridin-2(1H)-one (1.0 g, 3.9 mmol) and ethyl (2R)-4-bromo-2-methyl-2-(methylsulfonyl)butanoate, T1, (1.45 g, 5.06 mmol) in tetrahydrofuran:t-butanol (1:1, 50 mL). The resulting suspension was heated to reflux and was stirred at this temperature for 72 h. The reaction was filtered through celite, and the filter pad was washed with EtOAc (3×50 mL). The combined filtrates were concentrated and the crude product was purified via flash chromatography on an Analogix SF15-24 g column using an eluent of EtOAc in hexanes (0-50%) to afford the title compound as a yellow solid (575.6 mg, 32%). MS (LCMS) m/z 463.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (s, 3H) 1.58 (s, 3H) 2.20 (dt, J=13.90, 7.00 Hz, 1H) 2.52-2.62 (m, 1H) 3.14 (s, 3H) 4.00 (t, J=7.61 Hz, 2H) 4.05-4.22 (m, 2H) 7.94 (dd, J=4.20, 2.05 Hz, 1H).

Aufarbeitung

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux
  3. filtrationThe reaction was filtered through celite
  4. washthe filter pad was washed with EtOAc (3×50 mL)
  5. concentrationThe combined filtrates were concentrated
  6. customthe crude product was purified via flash chromatography on an Analogix SF15-24 g column

Quellen und Nachweise

ORD-Eintrag
ord-7d252824ca624984a0d3279a86c7e6d6
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08624034B2

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