2-(Di-tert-butylphosphino)biphenyl → (S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl ester

HRID 732365Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 732365
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:38][S:39]([NH2:42])(=[O:41])=[O:40].[Na]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([NH:42][S:39]([CH3:38])(=[O:41])=[O:40])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

Komponenten

6

Edukt 3

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 86614996HCID 86614996, VerbindungHCID 86614997HCID 86614997, Verbindung

Produkt 1

HCID 68814626(S)-2-sec-butylamino-6-methanesulfonylamino-isonicotinic acid methyl esterAusbeute 46,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
99 °C

Versuchsvorschrift

Add to a 300 mL of autoclave reactor (s)-(+)-2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (12.46 g, 0.05134 mol), bis(dibenzylideneacetone)-palladium (0) (2.35 g, 0.002567 mol), 2-di-tert-butylphosphino biphenyl (1.53 g, 0.005134 mol) and sodium methanesulfonamide (12.02 g, 0.1027 mol) in toluene (250 mL). Flush with nitrogen 3 times and heat to 99° C. for 24 h. Filter and dissolve the filter cake in water (400 mL). Extract the aqueous layer with chloroform (3×200 mL), dry (magnesium sulfate) and concentrate. Dissolve the crude product in dichloromethane (20 mL) and precipitate out by adding hexanes (400 mL) to give a solid (7.18 g, 46%). m.p. 118.6-123.0° C., 1H NMR (500 MHz, DMSO) δ 6.87 (s, 1H), 6.69 (s, 1H), 4.83 (br, 1H), 3.94 (s, 3H), 3.74 (m, 1H), 3.27 (s, 1H), 1.60 (m, 2H) 1.25 (d, J=7 Hz, 3H), 0.99 (t, J=7 Hz, 3H).

Aufarbeitung

  1. customFlush with nitrogen 3 times
  2. filtrationFilter
  3. dissolutiondissolve the filter cake in water (400 mL)
  4. extractionExtract the aqueous layer with chloroform (3×200 mL)
  5. dry with materialdry (magnesium sulfate)
  6. concentrationconcentrate
  7. dissolutionDissolve the crude product in dichloromethane (20 mL)
  8. customprecipitate out
  9. additionby adding hexanes (400 mL)

Quellen und Nachweise

ORD-Eintrag
ord-667f43aa396140229fc88d6a0f4ecf80
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07585885B2

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