Potassium Carbonate → 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotoluene

HRID 1027976Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1027976
[CH3:1][N:2]1[CH:6]2[CH2:7][NH:8][CH:4]([CH2:5]2)[CH2:3]1.Cl.Cl.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21].C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[CH3:1][N:2]1[CH2:3][C@@H:4]2[CH2:5][C@H:6]1[CH2:7][N:8]2[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=1[CH3:21]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 68001Benzene, 1-fluoro-2-methyl-4-nitro-HCID 229244032-Methyl-2,5-diaza-bicyclo[2.2.1]heptane dihydrochloride

Produkt 1

HCID 686324012-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-nitrotolueneAusbeute 74,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

Alternatively, (1S,4S)-2-Methyl-2,5-diazabicyclo[2.2.1]heptane.2HBr (24.8 g, 90.5 mmol), 2-fluoro-5-nitrotoluene (12.0 g, 77.3 mmol) and K2CO3 (43.7 g, 316.9 mmol) in 90 mL NMP were heated at 110° C. for 14 h by stirring. The reaction mixture was allowed to cool and quenched by pouring into water (500 mL). The contents were then stirred until precipitation was observed (3-4 h). The yellow solid formed was collected by filtration. The resulting filter cake washed with water (700 mL) and dried under vacuum suction. The filter cake was re-suspended in 10% EtOAc/hexanes (100 mL) as a slurry and then filtered to provide the desired material 2-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]-5-nitrotoluene (14.2 g, 74% based on nitrotoluene; 63% based on diazabicycloheptane) after drying; 1H NMR (DMSO-d6): δ 7.88-7.55 (m, 2H), 6.69 (d, 1H, J=8.8 Hz), 4.37 (s, 1H), 3.64 (dd, 1H, J=2.0 and 9.9 Hz), 3.38-3.55 (m, 2H), 2.81 (d, 1H, J=9.9 Hz), 2.65 (d, 1H, J=9.9 Hz), 2.33 (s, 3H), 2.23 (s, 3H), 1.87 (d, 1H, J=9.3 Hz), 1.75 (d, 1H, J=9.3 Hz). LCMS: purity: 98%; MS (m/e): 248 (MH+).

Aufarbeitung

  1. temperatureto cool
  2. customquenched
  3. additionby pouring into water (500 mL)
  4. stirringThe contents were then stirred until precipitation
  5. custom(3-4 h)
  6. customThe yellow solid formed
  7. filtrationwas collected by filtration
  8. filtrationThe resulting filter cake
  9. washwashed with water (700 mL)
  10. customdried under vacuum suction
  11. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-2cdbabd8d69240589005fa2a9610374c
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08735418B2

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