Pyridine → [4-(3-Aza-bicyclo[3.1.0]hex-3-yl)-3,5-difluoro-phenyl]-carbamic acid benzyl ester

HRID 1814031노트

반응식

HRID 1814031 반응식
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[C:4]([F:11])[C:3]=1[N:12]1[CH2:17][CH:16]2[CH:14]([CH2:15]2)[CH2:13]1.[Cl-].[NH4+].N1C=CC=CC=1.Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>C(O)C.O.ClCCl.[Fe]>[CH2:30]([O:29][C:27](=[O:28])[NH:8][C:6]1[CH:7]=[C:2]([F:1])[C:3]([N:12]2[CH2:17][CH:16]3[CH:14]([CH2:15]3)[CH2:13]2)=[C:4]([F:11])[CH:5]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

참가 물질

8

반응물 4

HCID 1049PyridineHCID 10387Benzyl chloroformateHCID 25517Ammonium ChlorideHCID 114249713-(2,6-Difluoro-4-nitro-phenyl)-3-aza-bicyclo[3.1.0]hexane

생성물 1

HCID 11290870[4-(3-Aza-bicyclo[3.1.0]hex-3-yl)-3,5-difluoro-phenyl]-carbamic acid benzyl ester

시약·촉매·용매 3

HCID 23925Iron촉매HCID 6344Dichloromethane용매2회HCID 19096565Water ethanol용매

반응 조건

온도
0 °C

실험 절차

Iron metal (0.120 g, 2.15 mmol) was added in five portions over 1 h to a refluxing solution of 3-(2,6-difluoro-4-nitro-phenyl)-3-aza-bicyclo[3.1.0]hexane (0.172 g, 0.72 mmol) and ammonium chloride (0.385 g, 7.2 mmol) in 6.0 mL of 2:1 ethanol-H2O. The rust colored mixture was refluxed for another 30 min and then cooled and filtered to remove iron oxide. H2O was added to the filtrate and the mixture concentrated to remove ethanol. The resulting aqueous solution was extracted with three 20 mL portions of ethyl acetate and the combined organic phases washed with H2O, brine, and dried (MgSO4). Filtration and concentration gave the crude amine (0.145 g, 0.69 mmol) which was dissolved in 5.0 mL of dichloromethane. Pyridine (0.111 mL, 1.38 mmol) was added to the amine solution and after cooling to 0° C., benzyl chloroformate (0.113 mL, 0.79 mmol) was added. The mixture was stirred for 30 min at 0° C. and for 30 min at room temperature. The reaction mixture was then diluted with dichloromethane and washed with H2O, brine and then dried (MgSO4). Concentration gave a yellow oil that was triturated with hexane to afford [4-(3-aza-bicyclo[3.1.0]hex-3-yl)-3,5-difluoro-phenyl]-carbamic acid benzyl ester as a yellow solid.

후처리

  1. temperaturecooled
  2. filtrationfiltered
  3. customto remove iron oxide
  4. additionH2O was added to the filtrate
  5. concentrationthe mixture concentrated
  6. customto remove ethanol
  7. extractionThe resulting aqueous solution was extracted with three 20 mL portions of ethyl acetate
  8. washthe combined organic phases washed with H2O, brine
  9. dry with materialdried (MgSO4)
  10. filtrationFiltration and concentration
  11. customgave the crude amine (0.145 g, 0.69 mmol) which
  12. washwashed with H2O, brine
  13. dry with materialdried (MgSO4)
  14. concentrationConcentration
  15. customgave a yellow oil that
  16. customwas triturated with hexane

출처 및 근거

ORD 기록
ord-5986c531e27e46c8a7149993dc49a98d
출처 데이터셋
uspto-grants-2005_04
특허 번호
US06875784B2

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