Dimethyl Sulfoxide → 7-[4-Nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane

HRID 335391

Reaktionsgleichung

Reaktionsgleichung von HRID 335391
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].CS(C)=O.Cl.[CH:26]12[NH:32][CH:29]([CH2:30][CH2:31]1)[CH2:28][CH2:27]2>CCOC(C)=O>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:32]2[CH:26]3[CH2:31][CH2:30][CH:29]2[CH2:28][CH2:27]3)=[CH:3][C:4]=1[C:11]([F:14])([F:13])[F:12])([O-:10])=[O:9]

Komponenten

6

Edukt 4

HCID 679Dimethyl SulfoxideHCID 10340Sodium CarbonateHCID 2230945-Fluoro-2-nitrobenzotrifluorideHCID 162795037-Azabicyclo[2.2.1]heptane hydrochloride

Produkt 1

HCID 575168437-[4-Nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

4-fluoro-1-nitro-2-(trifluoromethyl)benzene (7) (901 g, 4.309 mol) was introduced into a 30 L jacketed vessel along with Na2CO3 (959.1 g, 9.049 mol) and DMSO (5 L, 5.5 vol) under nitrogen atmosphere and stirring. 7-azabicyclo[2.2.1]heptane hydrochloride (8-HCl) (633.4 g, 4.740 mol) was then added to the vessel in portions. The temperature was gradually raised to 55° C. When the reaction was substantially complete, the mixture was diluted with 10 vol EtOAc and washed with water (5.5 vol) three times or until DMSO in the aqueous layer disappeared (HPLC). The organic layer was concentrated to 4 vol and then the solvent was swapped with cyclohexane until all the EtOAc was removed, and the total volume in the flask was about 4 vol containing cyclohexane. The reaction mixture was heated to 60° C. on a rotary evaporator for 30 min. Then the solution was cooled to room temperature with stirring or rotation for 3 h. When all the solid crystallized, the solution was concentrated to dryness to provide 7-[4-nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane (9).

Aufarbeitung

  1. washwashed with water (5.5 vol) three times or until DMSO in the aqueous layer
  2. concentrationThe organic layer was concentrated to 4 vol
  3. customwas removed
  4. additioncontaining cyclohexane
  5. temperatureThe reaction mixture was heated to 60° C. on a rotary evaporator for 30 min
  6. temperatureThen the solution was cooled to room temperature
  7. stirringwith stirring
  8. customWhen all the solid crystallized
  9. concentrationthe solution was concentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-72df13e9756240768e5793ce75278fc7
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08884018B2

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