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

HRID 335391

반응식

HRID 335391 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
55 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-72df13e9756240768e5793ce75278fc7
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08884018B2

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