Potassium Phosphate, Tribasic → Ethyl (2R)-4-{5-fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoate

HRID 468645

Reaktionsgleichung

Reaktionsgleichung von HRID 468645
[F:1][C:2]1[C:3](I)=[CH:4][C:5](=[O:21])[N:6]([CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=1.CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][C:34]([N:37]3[N:41]=[CH:40][CH:39]=[N:38]3)=[CH:33][CH:32]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC1CCCO1.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]1[C:3]([C:31]2[CH:36]=[CH:35][C:34]([N:37]3[N:41]=[CH:40][CH:39]=[N:38]3)=[CH:33][CH:32]=2)=[CH:4][C:5](=[O:21])[N:6]([CH2:8][CH2:9][C@@:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:7]=1

Komponenten

8

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 67249679Ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoateHCID 672515672-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2H-1,2,3-triazole

Produkt 1

HCID 86670651Ethyl (2R)-4-{5-fluoro-2-oxo-4-[4-(2H-1,2,3-triazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoateAusbeute 67,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittel2×HCID 73012-MethyltetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

Pd(dppf)Cl2 (484 mg, 0.59 mmol) was added to a mixture of ethyl (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate, T2, (2.20 g, 4.94 mmol), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-1,2,3-triazole (2.01 g, 7.41 mmol), and potassium phosphate (3.95 g, 14.8 mmol) in 2-methyltetrahydrofuran (200 mL) and deionized water (40 mL). The reaction was heated to 60° C. and was vigorously stirred at this temperature overnight. The reaction was diluted with EtOAc (100 mL) and water (100 mL) and was filtered through a celite pad (˜1 inch). The filter pad was washed with EtOAc (100 mL) and the filtrates were combined. The aqueous layer was separated and was extracted with EtOAc (2×100 mL). The combined organics were washed with brine (100 mL), dried (MgSO4), filtered and concentrated. The crude material was purified via flash chromatography using a Varian SF25-40 g column and an eluent of EtOAc in hexanes (30-100%) to afford the title compound as a yellow solid (1.54 g, 67.4%). MS (LCMS) m/z 463.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.23 (t, 3H) 1.62 (s, 3H) 2.18-2.32 (m, 1H) 2.52-2.66 (m, 1H) 3.16 (s, 3H) 3.92-4.07 (m, 2H) 4.08-4.24 (m, 2H) 6.59 (d, J=7.81 Hz, 1H) 7.72-7.84 (m, 2H) 8.10 (d, J=6.63 Hz, 1H) 8.12-8.17 (m, 2H) 8.18 (s, 2H).

Aufarbeitung

  1. filtrationwas filtered through a celite pad (˜1 inch)
  2. washThe filter pad was washed with EtOAc (100 mL)
  3. customThe aqueous layer was separated
  4. extractionwas extracted with EtOAc (2×100 mL)
  5. washThe combined organics were washed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified via flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-dca7c565ae7848afb167b2c0c84db1e2
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08624034B2

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